ORCID Profile
0000-0002-5331-6370
Current Organisation
University of Sydney
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Publisher: AMPCo
Date: 07-05-2018
DOI: 10.5694/MJA18.00199
Abstract: Clinical research has established exercise as a safe and effective intervention to counteract the adverse physical and psychological effects of cancer and its treatment. This article summarises the position of the Clinical Oncology Society of Australia (COSA) on the role of exercise in cancer care, taking into account the strengths and limitations of the evidence base. It provides guidance for all health professionals involved in the care of people with cancer about integrating exercise into routine cancer care. Main recommendations: COSA calls for: exercise to be embedded as part of standard practice in cancer care and to be viewed as an adjunct therapy that helps counteract the adverse effects of cancer and its treatment all members of the multidisciplinary cancer team to promote physical activity and recommend that people with cancer adhere to exercise guidelines and best practice cancer care to include referral to an accredited exercise physiologist or physiotherapist with experience in cancer care. Changes in management as a result of the guideline: COSA encourages all health professionals involved in the care of people with cancer to: discuss the role of exercise in cancer recovery recommend their patients adhere to exercise guidelines (avoid inactivity and progress towards at least 150 minutes of moderate intensity aerobic exercise and two to three moderate intensity resistance exercise sessions each week) and refer their patients to a health professional who specialises in the prescription and delivery of exercise (ie, accredited exercise physiologist or physiotherapist with experience in cancer care).
Publisher: Elsevier BV
Date: 05-2019
Publisher: Oxford University Press (OUP)
Date: 02-2018
DOI: 10.1111/BJD.15688
Publisher: Wiley
Date: 08-06-2017
DOI: 10.1111/PCMR.12594
Publisher: Frontiers Media SA
Date: 07-06-2021
DOI: 10.3389/FPSYG.2021.661190
Abstract: Purpose: Psychological interventions targeting fear of cancer recurrence (FCR) are effective in reducing fear and distress. Process evaluations are an important, yet scarce adjunct to published intervention trials, despite their utility in guiding the interpretation of study outcomes and optimizing intervention design for broader implementation. Accordingly, this paper reports the findings of a process evaluation conducted alongside a randomized controlled trial of a psychological intervention for melanoma patients. Methods: Men and women with a history of Stage 0–II melanoma at high-risk of developing new primary disease were recruited via High Risk Melanoma Clinics across Sydney, Australia and randomly allocated to receive the psychological intervention ( n = 80) or usual care ( n = 84). Intervention participants received a tailored psycho-educational resource and three in idual psychotherapeutic sessions delivered via telehealth. Qualitative and quantitative data on intervention context, processes, and delivery (reach, dose, and fidelity), and mechanisms of impact (participant responses, moderators of outcome) were collected from a range of sources, including participant surveys, psychotherapeutic session audio-recordings, and clinical records. Results: Almost all participants reported using the psycho-educational resource (97%), received all intended psychotherapy sessions (96%), and reported high satisfaction with both intervention components. Over 80% of participants would recommend the intervention to others, and a small proportion (4%) found discussion of melanoma-related experiences confronting. Perceived benefits included enhanced doctor-patient communication, talking more openly with family members about melanoma, and improved coping. Of potential moderators, only higher FCR severity at baseline (pre-intervention) was associated with greater reductions in FCR severity (primary outcome) at 6-month follow-up (primary endpoint). Conclusions: Findings support the acceptability and feasibility of a psychological intervention to reduce FCR amongst in iduals at high risk of developing another melanoma. Implementation into routine melanoma care is an imperative next step, with FCR screening recommended to identify those most likely to derive the greatest psychological benefit.
Publisher: BMJ
Date: 02-2020
DOI: 10.1136/BMJOPEN-2019-032636
Abstract: Sentinel lymph node biopsy (SLNB) is a diagnostic procedure developed in the 1990s. It is currently used to stage patients with primary cutaneous melanoma, provide prognostic information and guide management. The Australian Clinical Practice Guidelines state that SLNB should be considered for patients with cutaneous melanoma mm in thickness (or .8 mm with high-risk pathology features). Until recently, sentinel lymph node (SLN) status was used to identify patients who might benefit from a completion lymph node dissection, a procedure that is no longer routinely recommended. SLN status is now also being used to identify patients who might benefit from systemic adjuvant therapies such as anti-programmed cell death 1 (PD1) checkpoint inhibitor immunotherapy or BRAF-directed molecular targeted therapy, treatments that have significantly improved relapse-free survival for patients with resected stage III melanoma and improved overall survival of patients with unresectable stage III and stage IV melanoma. Australian and international data indicate that approximately half of eligible patients receive an SLNB. This mixed-methods study seeks to understand the structural, contextual and cultural factors affecting implementation of the SLNB guidelines. Data collection will include: (1) cross-sectional questionnaires and semistructured interviews with general practitioners and dermatologists (2) semistructured interviews with other healthcare professionals involved in the diagnosis and early definitive care of melanoma patients and key stakeholders including researchers, representatives of professional colleges, training organisations and consumer melanoma groups and (3) documentary analysis of documents from government, health services and non-government organisations. Descriptive analyses and multivariable regression models will be used to examine factors related to SLNB practices and attitudes. Qualitative data will be analysed using thematic analysis. Ethics approval has been granted by the University of Sydney. Results will be disseminated through publications and presentations to clinicians, patients, policymakers and researchers and will inform the development of strategies for implementing SLNB guidelines in Australia.
Publisher: Oxford University Press (OUP)
Date: 18-08-2021
DOI: 10.1111/BJD.20633
Publisher: Public Library of Science (PLoS)
Date: 19-03-2015
Publisher: Oxford University Press (OUP)
Date: 08-2007
DOI: 10.1093/AJE/KWM161
Abstract: The associations of dietary total carbohydrates, overall glycemic index, total dietary glycemic load, total sugars, total starch, and total fiber with endometrial cancer risk were analyzed among 288,428 women in the European Prospective Investigation into Cancer and Nutrition cohort (1992-2004), including 710 incident cases diagnosed during a mean 6.4 years of follow-up. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. There were no statistically significant associations with endometrial cancer risk for increasing quartile intakes of any of the exposure variables. However, in continuous models calibrated by using 24-hour recall values, the multivariable relative risks were 1.61 (95% confidence interval: 1.06, 2.45) per 100 g/day of total carbohydrates, 1.40 (95% confidence interval: 0.99, 1.99) per 50 units/day of total dietary glycemic load, and 1.36 (95% confidence interval: 1.05, 1.76) per 50 g/day of total sugars. These associations were stronger among women who had never used postmenopausal hormone therapy compared with ever users (total carbohydrates p(heterogeneity) = 0.04). Data suggest no association of overall glycemic index, total starch, and total fiber with risk, and a possible modest positive association of total carbohydrates, total dietary glycemic load, and total sugars with risk, particularly among never users of hormone replacement therapy.
Publisher: Oxford University Press (OUP)
Date: 30-06-2014
Publisher: Oxford University Press (OUP)
Date: 24-09-2023
DOI: 10.1093/IJE/DYAC179
Publisher: Elsevier BV
Date: 02-2021
Publisher: Springer Science and Business Media LLC
Date: 2008
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/HEX.12406
Publisher: Springer Science and Business Media LLC
Date: 12-02-2007
DOI: 10.1007/S10552-006-0113-8
Abstract: To examine the association between anthropometry and endometrial cancer, particularly by menopausal status and exogenous hormone use subgroups. Among 223,008 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, there were 567 incident endometrial cancer cases during 6.4 years of follow-up. The analysis was performed with Cox proportional hazards modeling. Weight, body mass index (BMI), waist and hip circumferences and waist-hip ratio (WHR) were strongly associated with increased risk of endometrial cancer. The relative risk (RR) for obese (BMI 30- < 40 kg/m(2)) compared to normal weight (BMI or = 40) was 3.02, 95% CI = 1.66-5.52. The RR for women with a waist circumference of > or =88 cm vs. or =20 kg compared with stable weight (+/-3 kg) increased risk independent of body weight at age 20 (RR = 1.75, 95% CI = 1.11-2.77). These associations were generally stronger for postmenopausal than premenopausal women, and oral contraceptives never-users than ever-users, and much stronger among never-users of hormone replacement therapy compared to ever-users. Obesity, abdominal adiposity, and adult weight gain were strongly associated with endometrial cancer risk. These associations were particularly evident among never-users of hormone replacement therapy.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2013
Publisher: Springer Science and Business Media LLC
Date: 27-07-2016
DOI: 10.1007/S00520-016-3339-3
Abstract: People with melanoma often report pervasive fears about cancer recurrence, unmet information needs, and difficulties accessing psychological care. Interventions addressing the supportive care needs of people with melanoma are rare, and needs are often overlooked. The study evaluated a newly developed, evidence-based, psycho-educational resource for people with melanoma. The evaluation study comprised three groups: adults at high risk of new primary disease due to multiple previous melanomas or one melanoma and dysplastic nevus syndrome (DNS), adults at moderate risk due to one previous melanoma and no DNS, and health professionals involved in melanoma care. Participants evaluated a 68-page psycho-educational booklet, Melanoma: Questions and Answers, developed by a multidisciplinary team in accordance with published evidence, clinical guidelines, and intervention development frameworks. The booklet comprised seven modules featuring information on melanoma diagnosis, treatment, prognosis, and ongoing clinical management risk factors and the role of genetic counseling services for melanoma psycho-education on emotional, behavioral, and cognitive responses to melanoma, including psycho-education on fear of cancer recurrence description of healthy coping responses a suite of tailored tools to support skin self-examination, doctor-patient communication, and identification of the signs and symptoms of anxiety and depression a list of community-based services and resources and tools to support melanoma-related record keeping and monitoring. Resource acceptability, relevance, quality, dissemination preferences, emotional responses, unmet information needs, and demographic characteristics were assessed. Nineteen melanoma survivors (response rate 50 %) and 10 health professionals (response rate 83 %) evaluated the resource. Responses were overwhelmingly positive the booklet was thoroughly read and highly rated in terms of quality and quantity of information, utility of health education tools, and capacity to address unmet needs. Ninety-five percent of melanoma survivors would recommend the booklet to others. Most preferred a paper-based format, provided by their treating doctor at diagnosis. Melanoma: Questions and Answers was feasible and acceptable and demonstrated a strong capacity to address the information and psycho-educational needs of people with melanoma at low fiscal cost.
Publisher: Oxford University Press (OUP)
Date: 03-2017
DOI: 10.1111/BJD.15331
Publisher: Springer Science and Business Media LLC
Date: 03-01-2018
DOI: 10.1245/S10434-017-6319-Z
Abstract: Follow-up practices after diagnosis and treatment of primary cutaneous melanoma vary considerably. We aimed to determine factors associated with recommendations for follow-up setting, frequency, skin surveillance, and concordance with clinical guidelines. The population-based Melanoma Patterns of Care study documented clinicians' recommendations for follow-up for 2148 patients diagnosed with primary cutaneous melanoma over a 12-month period (2006/2007) in New South Wales, Australia. Multivariate log binomial regression models adjusted for patient and lesion characteristics were used to examine factors associated with follow-up practices. Of 2158 melanomas, Breslow thickness was 3 months were more likely to be recommended for females, less likely for people living in rural compared with urban areas, and less likely for thicker (≥ 1 mm) melanomas compared with in situ melanomas. Skin self-examination was encouraged in 84% of consultations and was less likely to be recommended for patients ≥ 70 years (PR 0.88, 95% CI 0.84-0.93) and for those with thicker (≥ 1 mm) melanomas (PR 0.92, 95% CI 0.86-0.99). Only 1% of patients were referred for psychological care. Follow-up recommendations were generally consistent with Australian national guidelines for management of melanoma, however some variations could be targeted to improve patient outcomes.
Publisher: Oxford University Press (OUP)
Date: 25-07-2020
DOI: 10.1111/BJD.17990
Abstract: People with melanoma want and need effective interventions for living with fear of cancer recurrence (FCR). This study reports the 12-month outcomes of a brief, psychological intervention designed to reduce FCR in people at high risk of developing another primary melanoma compared with usual care. In this two-arm randomized controlled trial, adults previously diagnosed with stage 0, I or II melanoma were randomly allocated to the intervention (n = 80) or control (usual care) arm (n = 84). The trial was registered with the Australian and New Zealand Clinical Trials Registry on 19 March 2013 (registration: ACTRN12613000304730). The intervention comprised a 76-page psychoeducational resource and three in idually tailored, telephone-based sessions with a psychologist, scheduled at specific time points around participants' dermatological appointments. The primary outcome was the level of self-reported fear of new or recurrent melanoma assessed at 12 months postintervention using the severity subscale of the Fear of Cancer Recurrence Inventory. Compared with the control arm, the intervention group reported significantly lower FCR at 12 months postintervention the between-group mean difference was -1·41 for FCR severity [95% confidence interval (CI) -2·6 to -0·2 P = 0·02] and -1·32 for FCR triggers (95% CI -2·6 to -0·02 P = 0·04). The odds ratio for FCR severity scores ≥13 (54% intervention, 63% control) was 0·59 (95% CI 0·30-1·14, P = 0·12). There were no differences between groups in secondary outcomes, such as anxiety, depression or health-related quality of life. The previously reported 6-month benefits of this brief, patient-centred psychological intervention in reducing FCR were found to continue 12 months postintervention, with no known adverse effects, supporting implementation as part of routine melanoma care.
Publisher: Springer Science and Business Media LLC
Date: 05-01-2018
DOI: 10.1007/S40258-017-0368-0
Abstract: Specialised surveillance using total body photography and digital dermoscopy to monitor people at very high risk of developing a second or subsequent melanoma has been reported as cost effective. We aimed to estimate the 5-year healthcare budget impact of providing specialised surveillance for people at very high risk of subsequent melanoma from the perspective of the Australian healthcare system. A budget impact model was constructed to assess the costs of monitoring and potential savings compared with current routine care based on identification of patients at the time of a melanoma diagnosis. We used data from a published cost-effectiveness analysis of specialised surveillance, and Cancer Registry data, to estimate the patient population and healthcare costs for 2017-2021. When all eligible patients, estimated at 18% of patients with melanoma diagnosed annually in Australia, received specialised surveillance rather than routine care, the cumulative 5-year cost was estimated at $93.5 million Australian dollars ($AU) ($US 64 million) for specialised surveillance compared with $AU 120.7 million ($US 82.7 million) for routine care, delivering savings of $AU 27.2 million ($US 18.6 million). With a staggered introduction of 60% of eligible patients accessing surveillance in year 1, increasing to 90% in years 4 and 5, the cumulative cost over 5 years was estimated at $AU 98.1 million ($US 67.2 million), amounting to savings of $AU 22.6 million ($US 15.5 million) compared with routine care. Specialised melanoma surveillance is likely to provide substantial cost savings for the Australian healthcare system.
Publisher: BMJ
Date: 15-02-2011
Publisher: Wiley
Date: 05-12-2020
DOI: 10.1111/AJD.13518
Abstract: In melanoma management, sentinel lymph node biopsy (SLNB) is used to stage patients and to indicate prognosis. More recently, it has been used to select patients for adjuvant therapy. This study aimed to report knowledge of and attitudes towards SLNB for patients with melanoma among Australian dermatologists. Mixed methods study using cross‐sectional questionnaires ( n = 88) and semi‐structured interviews ( n = 13), May–September 2019. Of the dermatologists surveyed, 56% thought SLNB had an important role in melanoma management, 26% were unsure and 18% thought SLNB unimportant. Of the 92% who would discuss SLNB with their patients, the main stated value of SLNB was for assessing eligibility for adjuvant therapies (79%) only 60% indicated SLNB was of value for providing prognostic information, and just over half (53%) thought it could improve staging. Interview data indicated that attitudes towards SLNB are shifting among dermatologists, driven by data from landmark clinical trials and the influence of professional networks. Accordingly, interviewees adopted one of three positions in relation to SLNB: (a) believed in utility of SLNB and adhered to the guidelines (b) were unconvinced about utility of SLNB but adhered to the guidelines and (c) were unconvinced about utility of SLNB and did not adhere to the guidelines. Although most of the dermatologists surveyed were familiar with and follow the SLNB recommendations, some disagreement with and distrust of the recommendations was evident. Greater acceptance of the SLNB recommendations appeared to be driven by the improved outcomes demonstrated in stage III patients receiving adjuvant systemic therapy.
Publisher: American Medical Association (AMA)
Date: 2017
DOI: 10.1001/JAMADERMATOL.2016.3327
Abstract: The identification of a subgroup at higher risk of melanoma may assist in early diagnosis. To characterize melanoma patients and the clinical features associated with their melanomas according to patient risk factors: many nevi, history of previous melanoma, and family history of melanoma, to assist with improving the identification and treatment of a higher-risk subgroup. The Melanoma Patterns of Care study was a population-based observational study of physicians' reported treatment of 2727 patients diagnosed with an in situ or invasive primary melanoma over a 12-month period from October 2006 to 2007 conducted in New South Wales. Our analysis of these data took place from 2015 to 2016. Age at diagnosis and body site of melanoma. Of the 2727 patients with melanoma included, 1052 (39%) were defined as higher risk owing to a family history of melanoma, multiple primary melanomas, or many nevi. Compared with patients with melanoma who were at lower risk (ie, without any of these risk factors), the higher-risk group had a younger mean age at diagnosis (62 vs 65 years, P < .001), but this differed by risk factor (56 years for patients with a family history, 59 years for those with many nevi, and 69 years for those with a previous melanoma). These age differences were consistent across all body sites. Among higher-risk patients, those with many nevi were more likely to have melanoma on the trunk (41% vs 29%, P < .001), those with a family history of melanoma were more likely to have melanomas on the limbs (57% vs 42%, P < .001), and those with a personal history were more likely to have melanoma on the head and neck (21% vs 15%, P = .003). These findings suggest that a person's risk factor status could be used to tailor surveillance programs and education about skin self-examination.
Publisher: American Association for Cancer Research (AACR)
Date: 2009
Publisher: Springer Science and Business Media LLC
Date: 14-11-2018
DOI: 10.1038/S41467-018-06649-5
Abstract: The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 in iduals. We confirm known loci including MTAP , PLA2G6 , and IRF4 , and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1 , PPARGC1B , HDAC4 , FAM208B, DOCK8 , and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk ( KITLG an exception), while many melanoma risk loci do not alter nevus count. For ex le, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.
Publisher: Wiley
Date: 16-04-2021
DOI: 10.1111/AJD.13595
Abstract: Diagnostic tools such as dermoscopy, sequential digital dermoscopy imaging (SDDI), total body photography (TBP) and automated diagnostic tools are available to assist in early melanoma diagnosis. The use, accessibility and barriers of dermoscopy have been well studied however, there are few similar studies regarding SDDI, TBP and automated diagnostic tools. We aim to understand the use of these diagnostic aids amongst Australian general practitioners (GPs) and dermatologists. Between June 2019 and January 2020, GPs and dermatologists across Australia were invited to participate in an online survey. Surveys were distributed through GP and dermatology organisations. A total of 227 survey responses were received, 175 from GPs and 52 from dermatologists. Amongst GPs, 44.6% worked in a skin cancer clinic. Dermoscopy was used at least occasionally by 98.9% of all GPs. SDDI was used by 93.6% of skin cancer GPs, 80.8% of dermatologists and 45.3% of generalist GPs. TBP was used or recommended by 77.1% of generalist GPs, 82.3% of skin cancer GPs and 86.5% of dermatologists. The most common barriers to the use of TBP were cost, limited accessibility, poor patient compliance, and time required for both patients and doctors. Very few clinicians reported using automated diagnostic tools. There was an interest in future diagnostic aids for melanoma in 88% of GPs and dermatologists. Dermoscopy, SDDI and TBP were commonly used by responding Australian skin cancer GPs and dermatologists in this survey. Automated diagnostic tools were not reported to be used routinely. Several barriers were identified for use of TBP.
Publisher: Wiley
Date: 26-01-2016
DOI: 10.1002/PON.4075
Abstract: Although the effectiveness of many psychosocial interventions for people with cancer has been established, one barrier to implementation in routine clinical care is a lack of data on cost-effectiveness. We conducted a systematic review to assess the cost-effectiveness of psychosocial interventions for improving psychological adjustment among people with cancer. A systematic review of the literature, study appraisal and narrative synthesis. Eight studies involving 1668 patients were identified. Four of these reported outcomes in a cost per quality adjusted life year (QALY) framework. Six studies reported psychosocial interventions to be cost-effective for improving health-related quality of life, mood, pain, distress or fear of cancer progression, compared with usual care. Of the six psychosocial interventions identified as cost-effective, three were cognitive-behavioural therapy-based interventions, one was a nurse-delivered telephone follow-up plus educational group programme, one was a group-based exercise and psychosocial intervention and one was a series of 10 face-to-face or telephone-based in idual support sessions delivered by a nurse. The quality of studies assessed according to the Consensus Health Economic Criteria-list criteria was good overall however, some studies were limited by their choice of outcome measure and omission of important categories of costs. Several psychosocial interventions, particularly those based on cognitive-behavioural therapy, have been demonstrated to represent good value for money in cancer care. Future research should include a clear definition of the economic question, inclusion of all relevant costs, and consideration of utility-based quality of life measures for QALY estimation. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2017
Abstract: Clinical guidelines recommend that people at high risk of melanoma receive regular surveillance to improve survival through early detection. A specialized High Risk Clinic in Sydney, Australia was found to be effective for this purpose however, wider implementation of this clinical service requires evidence of cost-effectiveness and data addressing potential overtreatment of suspicious skin lesions. A decision-analytic model was built to compare the costs and benefits of specialized surveillance compared with standard care over a 10-year period, from a health system perspective. A high-risk standard care cohort was obtained using linked population data, comprising the Sax Institute’s 45 and Up cohort study, linked to Medicare Benefits Schedule claims data, the cancer registry, and hospital admissions data. Benefits were measured in quality-adjusted life-years gained. Sensitivity analyses were undertaken for all model parameters. Specialized surveillance through the High Risk Clinic was both less expensive and more effective than standard care. The mean saving was A$6,828 (95% CI, $5,564 to $8,092) per patient, and the mean quality-adjusted life-year gain was 0.31 (95% CI, 0.27 to 0.35). The main drivers of the differences were detection of melanoma at an earlier stage resulting in less extensive treatment and a lower annual mean excision rate for suspicious lesions in specialized surveillance (0.81 95% CI, 0.72 to 0.91) compared with standard care (2.55 95% CI, 2.34 to 2.76). The results were robust when tested in sensitivity analyses. Specialized surveillance was a cost-effective strategy for the management of in iduals at high risk of melanoma. There were also fewer invasive procedures in specialized surveillance compared with standard care in the community.
Publisher: MDPI AG
Date: 16-11-2021
DOI: 10.3390/CURRONCOL28060401
Abstract: Genome-wide association studies (GWAS) and candidate pathway studies have identified low-penetrant genetic variants associated with cutaneous melanoma. We investigated the association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival. The Genes, Environment, and Melanoma Study enrolled 3285 European origin participants with incident invasive primary melanoma. For each of 47 melanoma-risk single nucleotide polymorphisms (SNPs), we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and odds ratios for presence of ulceration, mitoses, and tumor-infiltrating lymphocytes (TILs). We also used Cox proportional hazards regression modeling to estimate the per allele hazard ratios for melanoma-specific survival. Passing the false discovery threshold (p = 0.0026) were associations of IRF4 rs12203592 and CCND1 rs1485993 with log of Breslow thickness, and association of TERT rs2242652 with presence of mitoses. IRF4 rs12203592 also had nominal associations (p 0.05) with presence of mitoses and melanoma-specific survival, as well as a borderline association (p = 0.07) with ulceration. CCND1 rs1485993 also had a borderline association with presence of mitoses (p = 0.06). MX2 rs45430 had nominal associations with log of Breslow thickness, presence of mitoses, and melanoma-specific survival. Our study indicates that further research investigating the associations of these genetic variants with underlying biologic pathways related to tumor progression is warranted.
Publisher: MDPI AG
Date: 12-10-2022
DOI: 10.3390/JPM12101704
Abstract: The evolution of polygenic scores for use in for disease prevention and control compels the development of guidelines to optimize their effectiveness and promote equitable use. Understanding the motivations and barriers to participation in genomics research can assist in drafting these standards. We investigated these in a community-based randomized controlled trial that examined the health behavioral impact of receiving personalized melanoma genomic risk information. We examined participant responses in a baseline questionnaire and conducted interviews post-trial participation. Motivations differed in two ways: (1) by gender, with those identifying as women placing greater importance on learning about their personal risk or familial risk, and how to reduce risk and (2) by age in relation to learning about personal risk, and fear of developing melanoma. A barrier to participation was distrust in the handling of genomic data. Our findings provide new insights into the motivations for participating in genomics research and highlight the need to better target population subgroups including younger men, which will aid in tailoring recruitment for future genomic studies.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2015
DOI: 10.1158/1055-9965.EPI-14-1203
Abstract: Background: Awareness of in idual risk may encourage improved prevention and early detection of melanoma. Methods: We evaluated the accuracy of self-reported pigmentation and nevus phenotype compared with clinical assessment, and examined agreement between nevus counts from selected anatomical regions. The s le included 456 cases with invasive cutaneous melanoma diagnosed between ages 18 to 39 years and 538 controls from the population-based Australian Melanoma Family Study. Participants completed a questionnaire about their pigmentation and nevus phenotype, and attended a dermatologic skin examination. Results: There was strong agreement between self-reported and clinical assessment of eye color [κ, = 0.78 95% confidence interval (CI), 0.74–0.81] and moderate agreement for hair color (κ = 0.46 95% CI, 0.42–0.50). Agreement between self-reported skin color and spectrophotometer-derived measurements was poor (κ = 0.12 95% CI, 0.08–0.16) to moderate (Spearman correlation rs = −0.37 95% CI, −0.32 to −0.42). Participants tended to underestimate their nevus counts and pigmentation men were more likely to underreport their skin color. The rs was 0.43 (95% CI, 0.38–0.49) comparing clinical total body nevus counts with self-reported nevus categories. There was good agreement between total body nevus counts and site-specific nevus counts, particularly on both arms. Conclusions: Young adults have suboptimal accuracy when assessing important risk characteristics including nevus numbers and pigmentation. Measuring nevus count on the arms is a good predictor of full body nevus count. Impact: These results have implications for the likely success of targeted public health programs that rely on self-assessment of these factors. Cancer Epidemiol Biomarkers Prev 24(4) 736–43. ©2015 AACR.
Publisher: American Medical Association (AMA)
Date: 2018
Publisher: Elsevier BV
Date: 06-2019
Publisher: JMIR Publications Inc.
Date: 20-12-2022
DOI: 10.2196/40623
Abstract: The growing number of melanoma patients who need long-term surveillance increasingly exceeds the capacity of the dermatology workforce, particularly outside of metropolitan areas. Digital technologies that enable patients to perform skin self-examination and send dermoscopic images of lesions of concern to a dermatologist (mobile teledermoscopy) are a potential solution. If these technologies and the remote delivery of melanoma surveillance are to be incorporated into routine clinical practice, they need to be accepted by clinicians providing melanoma care, such as dermatologists and general practitioners (GPs). This study aimed to explore perceptions of potential benefits and harms of mobile teledermoscopy, as well as experiences with this technology, among clinicians participating in a pilot randomized controlled trial (RCT) of patient-led melanoma surveillance. This qualitative study was nested within a pilot RCT conducted at dermatologist and skin specialist GP–led melanoma clinics in New South Wales, Australia. We conducted semistructured interviews with 8 of the total 11 clinicians who were involved in the trial, including 4 dermatologists (3 provided teledermatology, 2 were treating clinicians), 1 surgical oncologist, and 3 GPs with qualifications in skin cancer screening (the remaining 3 GPs declined an interview). Thematic analysis was used to analyze the data with reference to the concepts of “medical overuse” and “high-value care.” Clinicians identified several potential benefits, including increased access to dermatology services, earlier detection of melanomas, reassurance for patients between scheduled visits, and a reduction in unnecessary clinic visits. However, they also identified some potential concerns regarding the use of the technology and remote monitoring that could result in diagnostic uncertainty. These included poor image quality, difficulty making assessments from a 2D digital image (even if good quality), insufficient clinical history provided, and concern that suspicious lesions may have been missed by the patient. Clinicians thought that uncertainty arising from these concerns, together with perceived potential medicolegal consequences from missing a diagnosis, might lead to increases in unnecessary clinic visits and procedures. Strategies suggested for achieving high-value care included managing clinical uncertainty to decrease the potential for medical overuse and ensuring optimal placement of patient-led teledermoscopy within existing clinical care pathways to increase the potential for benefits. Clinicians were enthusiastic about the potential and experienced benefits of mobile teledermoscopy however, managing clinical uncertainty will be necessary to achieve these benefits in clinical care outside of trial contexts and minimize potential harms from medical overuse. Australian and New Zealand Clinical Trials Registry ACTRN12616001716459 anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371865
Publisher: Cold Spring Harbor Laboratory
Date: 07-08-2017
DOI: 10.1101/173112
Abstract: The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, United Kingdom, and United States, comprising a total of 52,506 phenotyped in iduals. We confirm known loci including MTAP , PLA2G6 , and IRF4 , and detect novel SNPs at a genome-wide level of significance in KITLG , DOCK8 , and a broad region of 9q32. In a bivariate analysis combining the nevus results with those from a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A , CYP1B1 , PPARGC1B , HDAC4 , FAM208B and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1 , reached a suggestive level of significance. Overall, we conclude that most nevus genes affect melanoma risk ( KITLG an exception), while many melanoma risk loci do not alter nevus count. For ex le, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis via genes we can show to be expressed under control of the MITF melanocytic cell lineage regulator.
Publisher: Wiley
Date: 04-06-2021
DOI: 10.1002/SKI2.51
Abstract: Non‐melanoma skin cancers (NMSCs) are common and consume many healthcare resources. A health utility is a single preference‐based value for assessing health‐related quality of life, which can be used in economic evaluations. There are scarce data on health utilities for NMSCs. Using a systematic review approach, we synthesized the current data on NMSC‐related health utilities. A systematic review of studies of NMSC‐related health utilities was conducted in Medline, Embase, and Cochrane databases. Data were extracted based on the protocol and a quality assessment was performed for each study. The protocol resulted in 16 studies, involving 121 621 participants. Mean utility values across the studies ranged from 0.56 to 1 for undifferentiated NMSC, 0.84 to 1 for actinic keratosis, 0.45 to 1 for squamous cell carcinoma, and 0.67 to 1 for basal cell carcinoma. There was considerable variability in utilities by type of cancer, stage of diagnosis, time to treatment, treatment modality, and quality of life instrument or method. Utility values were predominantly based on the EuroQol 5‐dimension instrument and ranged from 0.45 to 0.96, while other measurement methods produced values ranging from 0.67 to 1. Lower utility values were observed for advanced cancers and for the time period during and immediately after treatment, after which values gradually returned to pre‐treatment levels. Most utility values clustered around relatively high values of 0.8 to 1, suggesting small decrements in quality of life associated with most NMSCs and their precursors. Variability in utilities indicates that careful characterization is required for measures to be used in economic evaluations.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
Publisher: BMJ
Date: 09-2023
Publisher: Cambridge University Press (CUP)
Date: 08-2008
DOI: 10.1017/S0007114507898655
Abstract: We examined the association of dietary carbohydrates, protein, fat (including fatty acid subtypes) and alcohol with the metabolic syndrome and its components, in a cross-sectional study of 1626 patients with at least one cardiovascular risk factor. Multivariate nutrient density substitution models were used to examine the associations between macronutrients (assessed by 24 h dietary recall) and the metabolic syndrome. These models express the effects of ‘substituting’ one macronutrient for another without altering total energy intake. Increases in carbohydrates offset by isoenergetic decreases in either fat or protein were associated with a decrease in the prevalence of the metabolic syndrome (OR 0·87 (95 % CI 0·81, 0·93), P 0·0001 OR 0·70 (95 % CI 0·61, 0·79), P 0·0001, per 5 % energy intake respectively). Increased intake of dietary fat at the expense of dietary protein was also associated with a decreased prevalence of the metabolic syndrome (OR 0·80 (95 % CI 0·70, 0·92), P = 0·002 per 5 % energy intake). There were no statistically significant differences between fatty acid subtypes ( P ·10). Consumption of up to one standard alcoholic drink per d was associated with a lower prevalence of the metabolic syndrome when compared with non-drinkers (OR 0·67 (95 % CI 0·50, 0·89), P = 0·006) however, these benefits were weakened with higher levels of alcohol intake ( P = 0·10 for one to three drinks and P = 0·29 for three drinks). Thus, a diet high in carbohydrates, low in fat and protein, with low-to-moderate alcohol intake, is associated with a reduced prevalence of the metabolic syndrome.
Publisher: Oxford University Press (OUP)
Date: 17-10-2020
DOI: 10.1093/HMG/DDAA222
Abstract: Germline genetic variants have been identified, which predispose in iduals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness. To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness. The analyses utilized 10 604 in iduals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated in iduals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 in iduals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry. We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P & 5 × 10−8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion.
Publisher: Oxford University Press (OUP)
Date: 20-09-2018
DOI: 10.1111/BJD.17089
Publisher: Springer Science and Business Media LLC
Date: 11-03-2009
DOI: 10.1007/S10549-008-9958-8
Abstract: It is hypothesized that insulin resistance and related metabolic factors may influence breast cancer risk, however the epidemiological evidence remains inconclusive. We conducted a case-control study nested in a prospective cohort in Northern Sweden, to clarify the associations of body mass index (BMI), leptin, adiponectin, C-peptide, and glycated haemoglobin (HbA1c) with breast cancer risk. We also investigated whether these associations may be modified by age at diagnosis, tumour stage, and oestrogen and progesterone receptor status. During follow-up, 561 women developed invasive breast cancer and 561 matched controls were selected. Conditional logistic regression was used to calculate odds ratios (OR) as estimates of relative risk, and 95% confidence intervals (CI). The associations of BMI, leptin and HbA1c with breast cancer risk differed significantly according to whether the tumour was diagnosed as stage I or stage II-IV (P (heterogeneity) all <0.05). These factors were significantly inversely associated with risk in the group of stage I tumours, with ORs for top vs. bottom tertile for BMI of 0.48 (95% CI, 0.30-0.78, P (trend) = 0.004) leptin, 0.64 (95% CI, 0.41-1.00, P (trend) = 0.06) and HbA1c, 0.47 (95% CI, 0.28-0.80, P (trend) = 0.005). For stage II-IV tumours, there was a suggestion of an increased risk with higher levels of these factors. There were no significant differences in the associations of BMI, leptin, adiponectin, C-peptide and HbA1c with breast cancer risk in subgroups of age at diagnosis or tumour receptor status. This prospective study suggests that BMI, leptin and HbA1c influence breast tumour initiation and progression.
Publisher: JMIR Publications Inc.
Date: 23-12-0018
Abstract: urrent clinician-led melanoma surveillance models require frequent routinely scheduled clinic visits, with associated travel, cost, and time burden for patients. Patient-led surveillance is a new model of follow-up care that could reduce health care use such as clinic visits and medical procedures and their associated costs, increase access to care, and promote early diagnosis of a subsequent new melanoma after treatment of a primary melanoma. Understanding patient experiences may allow improvements in implementation. his study aims to explore patients’ experiences and perceptions of patient-led surveillance during the 6 months of participation in the MEL-SELF pilot randomized controlled trial. Patient-led surveillance comprised regular skin self-examination, use of a mobile dermatoscope to image lesions of concern, and a smartphone app to track and send images to a teledermatologist for review, in addition to usual care. emistructured interviews were conducted with patients previously treated for melanoma localized to the skin in New South Wales, Australia, who were randomized to the patient-led surveillance (intervention group) in the trial. Thematic analysis was used to analyze the data with reference to the technology acceptance model. e interviewed 20 patients (n=8, 40% women and n=12, 60% men median age 62 years). Patients who were more adherent experienced benefits such as increased awareness of their skin and improved skin self-examination practice, early detection of melanomas, and opportunities to be proactive in managing their clinical follow-up. Most participants experienced difficulty in obtaining clear images and technical problems with the app. These barriers were overcome or persevered by participants with previous experience with digital technology and with effective help from a skin check partner (such as a spouse, sibling, or friend). Having too many or too few moles decreased perceived usefulness. atients with melanoma are receptive to and experience benefits from patient-led surveillance using teledermoscopy. Increased provision of training and technical support to patients and their skin check partners may help to realize the full potential benefits of this new model of melanoma surveillance.
Publisher: Oxford University Press (OUP)
Date: 22-03-2023
DOI: 10.1093/BJD/LJAD076
Abstract: This cross-sectional survey identified risk factors for developing a second primary melanoma. Patients with melanoma who had characteristics such as male sex, older age, high naevus count, or melanoma on the trunk or upper limbs had a substantially higher risk of subsequent melanoma and should therefore be more intensively monitored.
Publisher: Wiley
Date: 26-11-2014
DOI: 10.1002/IJC.29317
Publisher: Oxford University Press (OUP)
Date: 03-11-2009
DOI: 10.1093/AJE/KWP307
Publisher: Wiley
Date: 26-09-2006
DOI: 10.1002/IJC.22125
Abstract: Research conducted predominantly in male populations on physical activity and lung cancer has yielded inconsistent results. We examined this relationship among 416,277 men and women from the European Prospective Investigation into Cancer and Nutrition (EPIC). Detailed information on recent recreational, household and occupational physical activity, smoking habits and diet was assessed at baseline between 1992 and 2000. Relative risks (RR) were estimated using Cox regression. During 6.3 years of follow-up we identified 607 men and 476 women with incident lung cancer. We did not observe an inverse association between recent occupational, recreational or household physical activity and lung cancer risk in either males or females. However, we found some reduction in lung cancer risk associated with sports in males (adjusted RR = 0.71 95% confidence interval 0.50-0.98 highest tertile vs. inactive group), cycling (RR = 0.73 0.54-0.99) in females and non-occupational vigorous physical activity. For occupational physical activity, lung cancer risk was increased for unemployed men (adjusted RR = 1.57 1.20-2.05) and men with standing occupations (RR = 1.35 1.02-1.79) compared with sitting professions. There was no evidence of heterogeneity of physical activity associations across countries, or across any of the considered cofactors. For some histologic subtypes suggestive sex-specific reductions, limited by subgroup sizes, were observed, especially with vigorous physical activity. In total, our study shows no consistent protective associations of physical activity with lung cancer risk. It can be assumed that the elevated risks found for occupational physical activity are not produced mechanistically by physical activity itself but rather reflect exposure to occupation-related lung cancer risk factors.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.EJPB.2016.01.015
Abstract: PurSil®AL20 (PUS), a copolymer of 4,4'-dicyclohexylmethane diisocyanate (HMDI), 1,4-butane diol (BD), poly-tetramethylene oxide (PTMO) and poly-dimethyl siloxane (PDMS) was investigated for stability as a vehicle for Docetaxel (DTX) delivery through oesophageal drug eluting stent (DES). On exposure to stability test conditions, it was found that DTX release rate declined at 4 and 40 °C. In order to ulge reasons underlying this, changes in DTX solid state as well as PUS microstructure were followed. It was found that re-crystallization of DTX in PDMS rich regions was reducing the drug release at both 4 °C and 40 °C s les. So far microstructural features have not been correlated with stability and drug release, and in this study we found that at 40 °C increase in microstructural domain sizes and the inter-domain distances (from ∼85 Å to 129 Å) were responsible for hindering the DTX release in addition to DTX re-crystallization.
Publisher: Wiley
Date: 08-2017
DOI: 10.1111/AJD.12530
Abstract: To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006. Of 2605 patients with localised melanoma, 1019 (39%) were defined as at higher risk due to the presence of one or more of the following factors: a family history of melanoma (11%), multiple primary melanomas (17%), or many naevi (24%). Compared to patients at lower risk, high risk patients were more likely to receive their initial care from a primary care physician (56% vs 50%, P = 0.002), have their melanoma detected during a routine skin check (40% vs 33%, P < 0.001), have their lesion assessed with dermoscopy (63% vs 56%, P = 0.002), and be encouraged to have skin surveillance (84% vs 77%, P < 0.001) and skin self-examination (87% vs 83%, P = 0.03). Higher socioeconomic status and urban residence were associated with patients at higher risk receiving initial treatment from a specialist doctor. Clinical management of higher risk patients was more likely to conform to clinical practice guidelines for diagnosis and skin surveillance than to melanoma patients at lower risk.
Publisher: Wiley
Date: 05-11-2017
DOI: 10.1111/PCMR.12653
Publisher: Oxford University Press (OUP)
Date: 11-12-2015
DOI: 10.1111/BJD.13403
Abstract: Understanding how in iduals at high-risk of primary cutaneous melanoma are best identified, screened and followed up will help optimize melanoma prevention strategies and clinical management. We conducted a systematic review of international clinical practice guidelines and documented the quality of supporting evidence for recommendations for clinical management of in iduals at high risk of melanoma. Guidelines published between January 2000 and July 2014 were identified from a systematic search of Medline, Embase and four guideline databases 34 guidelines from 20 countries were included. High-risk characteristics that were consistently reported included many melanocytic naevi, dysplastic naevi, family history, large congenital naevi, and Fitzpatrick Type I and II skin types. Most guidelines identify risk factors and recommend that in iduals at high risk of cutaneous melanoma be monitored, but only half of the guidelines provide recommendations for screening based on level of risk. There is disagreement in screening and follow-up recommendations for those with an increased risk of future melanoma. High-level evidence supports long-term screening of in iduals at high risk and monitoring using dermoscopy. Evidence is low for defining screening intervals and duration of follow-up, and for skin self-examination, although education about skin self-examination is widely encouraged. Clinical practice guidelines would benefit from a dedicated section for identification, screening and follow-up of in iduals at high risk of melanoma. Guidelines could be improved with clear definitions of multiple naevi, family history and frequency of follow-up. Research examining the benefits and costs of alternative management strategies for groups at high risk will enhance the quality of recommendations.
Publisher: Wiley
Date: 17-10-2016
DOI: 10.1002/CAM4.929
Publisher: Royal College of General Practitioners
Date: 19-02-2019
DOI: 10.3399/BJGPOPEN18X101633
Abstract: As part of a pilot randomised controlled trial examining the impact of personal melanoma genomic risk information on behavioural and psychosocial outcomes, GPs were sent a booklet containing their patient’s genomic risk of melanoma. Using this booklet as an ex le of genomic risk information that might be offered on a population-level in the future, this study explored GP attitudes towards communicating genomic risk information and resources needed to support this process. Semi-structured interviews were conducted with 22 Australian GPs. The interviews were recorded and transcribed, and data were analysed thematically. GPs in this s le believed that communicating genomic risk may become a responsibility within primary care and they recommended a shared decisionmaking approach to guide the testing process. Factors were identified that may influence how and when GPs communicate genomic risk information. GPs view genomics-based risk as one of many disease risk factors and feel that this type of information could be applied in practice in the context of overall risk assessment for diseases for which prevention and early detection strategies are available. They believe it is important to ensure that patients understand their genomic risk and do not experience long-term adverse psychological responses. GPs desire clinical practice guidelines that specify recommendations for genomic risk assessment and patient management, point-of-care resources, and risk prediction tools that include genomic and traditional risk factors. These findings will inform the development of resources for preparing GPs to manage and implement genomic risk information in practice.
Publisher: American Medical Association (AMA)
Date: 06-2015
Publisher: Elsevier BV
Date: 11-2018
Publisher: Springer Berlin Heidelberg
Date: 2011
DOI: 10.1007/978-3-642-04231-7_7
Abstract: This chapter reviews the findings from epidemiologic studies of the associations of physical activity with gynecologic cancers, including those of the endometrium, ovaries, and cervix, and the biologic mechanisms mediating the associations. The epidemiologic evidence to date suggests that physical activity probably protects against endometrial cancer, with a risk reduction of about 20-30% for those with the highest levels of physical activity compared to those with the lowest levels, and that light to moderate physical activity including housework, gardening, or walking for transportation may reduce risk. The role of physical activity in ovarian cancer development remains uncertain, as findings from these studies have been inconsistent with about half the studies suggesting physical activity modestly decreases risk and about half the studies suggesting no association. A recent meta-analysis of studies examining recreational physical activity with ovarian cancer risk estimated a 20% reduced risk for the most active versus least active women. There is mounting evidence that sedentary behaviors such as sitting time probably increase risk of endometrial and ovarian cancers. Overall, there is insufficient evidence to draw a conclusion on a possible role of physical activity in the development of cervical cancer, although a modest influence on risk is possible through effects on sex steroid hormones and immune function. The biologic evidence provides strong support for a protective role of physical activity on cancer of the endometrium, and moderate support for cancer of the ovaries, as these cancers have a strong hormonal etiology. The more established biologic mechanisms that are supported by epidemiologic and experimental data involve endogenous sex hormone levels, insulin-mediated pathways, and maintenance of energy balance.In this chapter, we will discuss the evidence for an association of physical activity with gynecologic cancers including those of the endometrium, ovaries, and cervix. Cancers of the endometrium and ovaries have a strong hormonal etiology (Risch 1998 Kaaks et al. 2002 Lukanova and Kaaks 2005), and physical activity has been postulated as a potential modifiable risk factor for prevention of these cancers because it can influence circulating hormone levels, energy balance, and insulin-mediated pathways that are thought to be important mediators underlying the associations. Few studies have evaluated the association of physical activity with cervical cancer because the main causal factor is infection with certain types of human papillomavirus (HPV), although other hormonal and immune factors are also thought to play a role (Smith et al. 2003 Waggoner 2003). We review the findings from epidemiologic studies that have examined the associations of physical activity with gynecologic cancers, and the biologic mechanisms that might mediate the associations.
Publisher: Wiley
Date: 26-07-2007
DOI: 10.1002/IJC.22990
Abstract: Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54 95% CI = 1.47-4.38 and HR = 2.23 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.
Publisher: Wiley
Date: 09-10-2019
DOI: 10.1111/AJD.12928
Abstract: There are limited population-based data documenting the incidence and management of lentigo maligna (LM) and invasive lentigo maligna melanoma (LMM). We report the data on occurrence and management of LM and LMM in an Australian population. Prospective collection of incidence and clinician-reported management of melanoma in situ (MIS n = 450, capped) and localised invasive melanoma (n = 3251) notified to the New South Wales Cancer Registry over 12-months in 2006-2007. The estimated annual incidence of all MIS was 27.0 per 100 000 (LM 12.2, non-LM MIS 5.9 and unclassified MIS 9.0). Patients with LM or LMM were on average approximately 10 years older than those with other melanoma subtypes (P < 0.001). The head and neck was the location of 59% of LM, 44% of LMM and <20% of other melanoma subtypes (P < 0.001). The majority of LM and LMM were treated only by specialists. Diagnostic partial biopsies were more frequent for LM and LMM than for other melanoma subtypes, and primary care physicians were more likely than specialists to do a punch partial biopsy than a shave biopsy. The reported median definitive excision margin for LM was 5.0 mm compared with 7.2 mm for non-LM MIS (P = 0.001). In this Australian population, LM was twice as frequent as other types of MIS. Improved strategies for diagnosis and management are required.
Publisher: Wiley
Date: 22-10-2015
DOI: 10.1002/PON.4018
Abstract: Classical psychometric methods have been used to demonstrate the validity and reliability of the 42-item Fear of Cancer Recurrence Inventory (FCRI). Our aim was to expand on this evidence with information on the discriminative value of the in idual items when administered to people with a personal history of melanoma, using an item response theory (IRT) approach. We used a two-parameter IRT model to examine all items of the FCRI, primarily regarding whether people with a personal history of melanoma use the response scale as expected (as indicated by item characteristic curves), and whether the items can discriminate between those low and high on the constructs assessed by the instrument. The s le was comprised of 286 adults with a personal history of melanoma (58% male, mean age: 59.1 years). The established factor structure of the FCRI was generally confirmed. IRT highlighted several items with problematic item characteristic curves, including most items in the Reassurance and Coping Strategies domains. Several other items exhibited poor discrimination. Based on this IRT analysis, we outline suggestions for refinement of the FCRI and potential development of a short-form, that could reduce respondent burden. Generalisability of these findings beyond melanoma warrants further examination. Copyright © 2015 John Wiley & Sons, Ltd.
Publisher: Oxford University Press (OUP)
Date: 27-07-2020
DOI: 10.1093/HMG/DDAA156
Abstract: Cancers, including cutaneous melanoma, can cluster in families. In addition to environmental etiological factors such as ultraviolet radiation, cutaneous melanoma has a strong genetic component. Genetic risks for cutaneous melanoma range from rare, high-penetrance mutations to common, low-penetrance variants. Known high-penetrance mutations account for only about half of all densely affected cutaneous melanoma families, and the causes of familial clustering in the remainder are unknown. We hypothesize that some clustering is due to the cumulative effect of a large number of variants of in idually small effect. Common, low-penetrance genetic risk variants can be combined into polygenic risk scores. We used a polygenic risk score for cutaneous melanoma to compare families without known high-penetrance mutations with unrelated melanoma cases and melanoma-free controls. Family members had significantly higher mean polygenic load for cutaneous melanoma than unrelated cases or melanoma-free healthy controls (Bonferroni-corrected t-test P = 1.5 × 10−5 and 6.3 × 10−45, respectively). Whole genome sequencing of germline DNA from 51 members of 21 families with low polygenic risk for melanoma identified a CDKN2A p.G101W mutation in a single family but no other candidate high-penetrance melanoma susceptibility genes. This work provides further evidence that melanoma, like many other common complex disorders, can arise from the joint action of multiple predisposing factors, including rare high-penetrance mutations, as well as via a combination of large numbers of alleles of small effect.
Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 21-06-2019
DOI: 10.1007/S40258-019-00483-6
Abstract: This study aimed to evaluate the cost effectiveness of a newly developed psycho-educational intervention to reduce fear of cancer recurrence (FCR) in early-stage melanoma patients. A within-trial cost-effectiveness and cost-utility analysis was conducted from the Australian health system perspective using data from linked Medicare records. Outcomes included FCR, measured with the severity subscale of the FCR Inventory quality-adjusted life years (QALYs) measured using the preference-based instrument, Assessment of Quality of Life-8 Dimensions (AQoL-8D) and 12-month survival. An incremental cost-effectiveness ratio (ICER) was calculated for two economic outcomes: (1) cost per additional case of 'high' FCR avoided and (2) cost per QALY gained. Means and 95% CIs around the ICER were generated from non-parametric bootstrapping with 1000 replications. A total of 151 trial participants were included in the economic evaluation. The mean cost of the psycho-educational intervention was AU$1614 per participant, including intervention development costs. The ICER per case of high FCR avoided was AU$12,903. The cost-effectiveness acceptability curve demonstrated a 78% probability of the intervention being cost effective relative to the control at a threshold of AU$50,000 per extra person avoiding FCR. The ICER per QALY gained was AU$116,126 and the probability of the intervention being cost effective for this outcome was 36% at a willingness to pay of AU$50,000 per QALY. The psycho-educational intervention reduced FCR at 12 months for people at high risk of developing another melanoma and may represent good value for money. For the QALY outcome, the psycho-educational intervention is unlikely to be cost effective at standard government willingness-to-pay levels. The trial was prospectively registered in the Australian and New Zealand Clinical Trials Registry (CTRN12613000304730).
Publisher: Springer Science and Business Media LLC
Date: 04-05-2021
DOI: 10.1186/S13063-021-05231-7
Abstract: Most subsequent new primary or recurrent melanomas might be self-detected if patients are trained to systematically self-examine their skin and have access to timely medical review (patient-led surveillance). Routinely scheduled clinic visits (clinician-led surveillance) is resource-intensive and has not been shown to improve health outcomes fewer visits may be possible if patient-led surveillance is shown to be safe and effective. The MEL-SELF trial is a randomised controlled trial comparing patient-led surveillance with clinician-led surveillance in people who have been previously treated for localised melanoma. Stage 0/I/II melanoma patients ( n = 600) from dermatology, surgical, or general practice clinics in NSW Australia, will be randomised (1:1) to the intervention (patient-led surveillance, n = 300) or control (usual care, n = 300). Patients in the intervention will undergo a second randomisation 1:1 to polarised ( n = 150) or non-polarised ( n = 150) dermatoscope. Patient-led surveillance comprises an educational booklet, skin self-examination (SSE) instructional videos 3-monthly email/SMS reminders to perform SSE patient-performed dermoscopy with teledermatologist feedback clinical review of positive teledermoscopy through fast-tracked unscheduled clinic visits and routinely scheduled clinic visits following each clinician’s usual practice. Clinician-led surveillance comprises an educational booklet and routinely scheduled clinic visits following each clinician’s usual practice. The primary outcome, measured at 12 months, is the proportion of participants diagnosed with a subsequent new primary or recurrent melanoma at an unscheduled clinic visit. Secondary outcomes include time from randomisation to diagnosis (of a subsequent new primary or recurrent melanoma and of a new keratinocyte cancer), clinicopathological characteristics of subsequent new primary or recurrent melanomas (including AJCC stage), psychological outcomes, and healthcare use. A nested qualitative study will include interviews with patients and clinicians, and a costing study we will compare costs from a societal perspective. We will compare the technical performance of two different models of dermatoscope (polarised vs non-polarised). The findings from this study may inform guidance on evidence-based follow-up care, that maximises early detection of subsequent new primary or recurrent melanoma and patient wellbeing, while minimising costs to patients, health systems, and society. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000176864 . Registered on 18 February 2021.
Publisher: Wiley
Date: 28-02-2020
DOI: 10.1002/IJC.32930
Publisher: Elsevier BV
Date: 09-2018
Publisher: Springer Science and Business Media LLC
Date: 07-04-2011
DOI: 10.1007/S10552-011-9762-3
Abstract: To examine associations between early-life sun exposure and risk of invasive cutaneous melanoma diagnosed between ages 18 and 39 years. Data were analysed from 606 cases and 481 controls from the Australian Melanoma Family Study, a population-based, case-control-family study. Self- and parent-reported sun exposure was collected by interview. Odds ratios (OR) were estimated using unconditional logistic regression, adjusted for potential confounders. Self-reported childhood total sun exposure was not associated with melanoma overall, but was positively associated with melanoma diagnosed at 18-29 years of age (OR for highest vs. lowest quartile: 3.21, 95% confidence intervals (CI) 1.38-7.44 P (trend) 0.02 P (interaction) by age group 0.09). Analyses restricted to participants whose self-reported sun exposure was concordant with that recalled by their parents gave an OR for the highest versus lowest tertile of childhood total sun exposure of 2.28 (95% CI 1.03-5.04 P (trend) 0.05), and for any versus no severe childhood sunburn of 2.36 (95% CI 1.05-5.31). The association of self-reported severe sunburn with melanoma was evident only in people who tended to tan rather than burn and in people who had few nevi. The association of early-life sun exposure with early-onset melanoma is influenced by host factors.
Publisher: Bioscientifica
Date: 09-2007
DOI: 10.1677/ERC-07-0132
Abstract: To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set s ling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (RR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38–0.97), P trend = 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% CI 0.99–2.90), P trend = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% CI 1.46–4.66), P trend = 0.0006, P heterogeneity = 0.13) and never-users of exogenous hormones ( P heterogeneity = 0.005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51–2.97)), which increased with the number of MetS factors ( P trend = 0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median ( P interaction = 0.01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
Publisher: American Association for Cancer Research (AACR)
Date: 31-05-2015
DOI: 10.1158/1055-9965.EPI-14-1426
Abstract: Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case–control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma. Cancer Epidemiol Biomarkers Prev 24(6) 992–7. ©2015 AACR.
Publisher: Elsevier BV
Date: 03-2020
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000439246
Abstract: b i Aim: /i /b To explore the potential emotional and behavioural impact of providing information on personalised genomic risk to the public, using melanoma as an ex le, to aid research translation. b i Methods: /i /b We conducted four focus groups in which 34 participants were presented with a hypothetical scenario of an in idual's lifetime genomic risk of melanoma (using the term ‘genetic risk'). We asked about understanding of genetic risk, who would choose to receive this risk information, potential emotional and behavioural impacts, and other concerns or potential benefits. Data were analysed thematically. b i Results: /i /b Participants thought this risk information could potentially motivate preventive behaviours such as sun protection and related it to screening for other diseases including breast cancer. Factors identified as influencing the decision to receive genetic risk information included education level, children, age and gender. Participants identified potential negative impacts on the recipient such as anxiety and worry, and proposed that this could be mitigated by providing additional explanatory and prevention information, and contact details of a health professional for further discussion. Participants' concerns included workplace and insurance discrimination. b i Conclusion: /i /b Participants recognised the potential for both positive and negative emotional and behavioural impacts related to receiving information on the personalised genomic risk of melanoma.
Publisher: The Royal Australian College of General Practitioners
Date: 06-2020
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.CANEP.2016.09.006
Abstract: Guidelines recommend that health professionals identify and manage in iduals at high risk of developing melanoma, but there is limited population-based evidence demonstrating real-world practices. A population-based, observational study was conducted in the state of New South Wales, Australia to determine doctors' knowledge of melanoma patients' risk and to identify factors associated with better identification and clinical management. Data were analysed for 1889 patients with invasive, localised melanoma in the Melanoma Patterns of Care study. This study collected data on all melanoma diagnoses notified to the state's cancer registry during a 12-month period from 2006 to 2007, as well as questionnaire data from the doctors involved in their care. Three-quarters (74%) of patients had doctors who were aware of their risk factor status with respect to personal and family history of melanoma and the presence of many moles. Doctors working in general practice, skin cancer clinics and dermatology settings had better knowledge of patients' risk factors than plastic surgeons. Doctors were 15% more likely to know the family history of younger melanoma patients (<40years) than of those ≥80 years (95% confidence interval 4-26%). Early detection-related follow-up advice was more likely to be given to younger patients, by doctors aware of their patients' risk status, by doctors practising in plastic surgery, dermatology and skin cancer clinic settings, and by female doctors. Both patient-related and doctor-related factors were associated with doctors' recognition and management of melanoma patients' risk and could be the focus of strategies for improving care.
Publisher: Wiley
Date: 29-11-2013
DOI: 10.1002/IJC.28603
Publisher: Elsevier BV
Date: 08-2012
Publisher: Oxford University Press (OUP)
Date: 06-2019
DOI: 10.1111/BJD.17582
Abstract: There is a need for greater understanding of the spectrum of emotional and behavioural reactions that in iduals in the general population may experience in response to genomic testing for melanoma risk. To explore how in iduals in the general population respond to receiving personalized genomic risk of melanoma. Semistructured interviews were undertaken with 30 participants (aged 24-69 years, 50% female, 12 low risk, eight average risk, 10 high risk) recruited from a pilot trial in which they received personalized melanoma genomic risk information. We explored participants' emotional and behavioural responses to receiving their melanoma genomic risk information. The qualitative data were analysed thematically. Many participants reported a positive response to receiving their melanoma genomic risk, including feelings of happiness, reassurance and gaining new knowledge to help manage their melanoma risk. Some participants reported short-term negative emotional reactions that dissipated over time. Most in iduals, particularly those who received average or high-risk results, reported making positive behaviour changes to reduce their melanoma risk. Emotional and behavioural responses were linked to participants' expectations for their risk result, their pre-existing perception of their own melanoma risk, their existing melanoma preventive behaviours and their genomic risk category. Personalized melanoma genomic risk information alongside education and lifestyle counselling is favourably received by people without a personal history and unselected for a family history of melanoma. Participants described increased knowledge and awareness around managing skin cancer risk and improved sun protection and skin examination behaviours. Any initial feelings of distress usually dissipated over time.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2018
Publisher: Elsevier BV
Date: 12-2017
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.CANEP.2017.04.004
Abstract: Sunlight has been known as an important cause of skin cancer since around the turn of the 20th Century. A 1977 landmark paper of US scientists Fears, Scotto, and Schneiderman advanced a novel hypothesis whereby cutaneous melanoma was primarily caused by intermittent sun exposure (i.e. periodic, brief episodes of exposure to high-intensity ultraviolet radiation) while the keratinocyte cancers, squamous cell carcinoma and basal cell carcinoma, were primarily caused by progressive accumulation of sun exposure. With respect to cutaneous melanoma, this became known as the intermittent exposure hypothesis. The hypothesis stemmed from analysis of measured ambient ultraviolet radiation and age-specific incidence rates of melanoma and keratinocyte cancers collected as an extension to the US Third National Cancer Survey in several US States. In this perspective paper, we put this novel hypothesis into the context of knowledge at the time, and describe subsequent epidemiological and molecular research into melanoma that elaborated the intermittent exposure hypothesis and ultimately replaced it with a dual pathway hypothesis. Our present understanding is of two distinct biological pathways by which cutaneous melanoma might develop a nevus prone pathway initiated by early sun exposure and promoted by intermittent sun exposure or possibly host factors and a chronic sun exposure pathway in sun sensitive people who progressively accumulate sun exposure to the sites of future melanomas.
Publisher: American Association for Cancer Research (AACR)
Date: 04-10-2021
DOI: 10.1158/1055-9965.EPI-21-0686
Abstract: Genome-wide association studies have reported that genetic variation at ANRIL (CDKN2B-AS1) is associated with risk of several chronic diseases including coronary artery disease, coronary artery calcification, myocardial infarction, and type 2 diabetes mellitus. ANRIL is located at the CDKN2A/B locus, which encodes multiple melanoma tumor suppressors. We investigated the association of these variants with melanoma prognostic characteristics. The Genes, Environment, and Melanoma Study enrolled 3,285 European origin participants with incident invasive primary melanoma. For each of ten disease-associated SNPs at or near ANRIL, we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and ORs for presence of ulceration and tumor-infiltrating lymphocytes (TIL). We also assessed effect modification by tumor NRAS/BRAF mutational status. Rs518394, rs10965215, and rs564398 passed false discovery and were each associated (P ≤ 0.005) with TILs, although only rs564398 was independently associated (P = 0.0005) with TILs. Stratified by NRAS/BRAF mutational status, rs564398*A was significantly positively associated with TILs among NRAS/BRAF mutant, but not wild-type, cases. We did not find SNP associations with Breslow thickness or ulceration. ANRIL rs564398 was associated with TIL presence in primary melanomas, and this association may be limited to NRAS/BRAF-mutant cases. Pathways related to ANRIL variants warrant exploration in relationship to TILs in melanoma, especially given the impact of TILs on immunotherapy and survival.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CANEP.2019.05.002
Abstract: Exposure to ultraviolet radiation from sunlight is directly associated with melanoma skin cancer, however reducing sun-exposure can be difficult to achieve at a population level. Using a genomic risk information behaviour change trial for melanoma prevention, we classified participants as risk-seeking, risk-neutral or risk-averse for domain-specific risk taking (DOSPERT). One-way ANOVA determined the association between socio-demographic characteristics and risk-taking score, and multivariable linear regression ascertained impact of an in idual's underlying risk propensity on an objective measure of sun-exposure, standard erythemal dose (SED), at 3-months follow-up. Of 119 participants, mean age 53 years 50% males, 87% had a personal/family history of cancer 19% were classified risk-seeking, 57% risk-neutral. The mean risk-taking score was significantly higher in younger participants (≤50 years: 13.86 vs. >50 years: 11.11, p = 0.003) and lower in those with a personal/family history of skin cancer versus without (10.55 vs 13.33, p = 0.009). Risk averse in iduals had lower weekly mean SEDs at 3-months than risk neutral and risk seeking in iduals (2.56, 5.81, 4.81 respectively, p = 0.01). Risk seekers showed fewer sun protective habits (p < 0.001) and higher intentional tanning, (p = 0.01). At 3-months, risk seekers attained 16%-54% lower SEDs in the genomic information group compared with controls, however this was not significantly different across risk groups (interaction p = 0.13). An in idual's underlying risk attitude is likely associated with sun-exposure behaviours, and may modify the effect of a genomic risk information behaviour change intervention. Young people and risk seekers may benefit most from being given information on their genetic risk of melanoma.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2020
DOI: 10.1158/1055-9965.EPI-20-0595
Abstract: Scalp and neck (SN) melanoma confers a worse prognosis than melanoma of other sites but little is known about its determinants. We aimed to identify associations between SN melanoma and known risk genes, phenotypic traits, and sun exposure patterns. Participants were cases from the Western Australian Melanoma Health Study (n = 1,200) and the Genes, Environment, and Melanoma Study (n = 3,280). Associations between risk factors and SN melanoma, compared with truncal and arm/leg melanoma, were investigated using binomial logistic regression. Facial melanoma was also compared with the trunk and extremities, to evaluate whether associations were subregion specific, or reflective of the whole head/neck region. Compared with other sites, increased odds of SN and facial melanoma were observed in older in iduals [SN: OR = 1.28, 95% confidence interval (CI) = 0.92–1.80, Ptrend = 0.016 Face: OR = 4.57, 95% CI = 3.34–6.35, Ptrend & 0.001] and those carrying IRF4-rs12203592*T (SN: OR = 1.35, 95% CI = 1.12–1.63, Ptrend = 0.002 Face: OR = 1.29, 95% CI = 1.10–1.50, Ptrend = 0.001). Decreased odds were observed for females (SN: OR = 0.49, 95% CI = 0.37–0.64, P & 0.001 Face: OR = 0.66, 95% CI = 0.53–0.82, P & 0.001) and the presence of nevi (SN: OR = 0.66, 95% CI = 0.49–0.89, P = 0.006 Face: OR = 0.65, 95% CI = 0.52–0.83, P & 0.001). Differences observed between SN melanoma and other sites were also observed for facial melanoma. Factors previously associated with the broader head and neck region, notably older age, may be driven by the facial subregion. A novel finding was the association of IRF4-rs12203592 with both SN and facial melanoma. Understanding the epidemiology of site-specific melanoma will enable tailored strategies for risk factor reduction and site-specific screening c aigns.
Publisher: BMJ
Date: 10-2016
Publisher: Wiley
Date: 28-07-2011
DOI: 10.1002/IJC.25576
Abstract: Sunbed use is associated with increased risk of melanoma. Younger people might be more susceptible to the carcinogenic effects of ultraviolet radiation. We investigated the association between sunbed use and risk of early‐onset cutaneous malignant melanoma. From the Australian Melanoma Family Study, a multicentre, population‐based, case‐control‐family study, we analysed data for 604 cases diagnosed between ages 18 and 39 years and 479 controls. Data were collected by interview. Associations were estimated as odds ratios (ORs) using unconditional logistic regression, adjusting for age, sex, city, education, family history, skin color, usual skin response to sunlight and sun exposure. Compared with having never used a sunbed, the OR for melanoma associated with ever‐use was 1.41 (95% confidence interval (CI) 1.01–1.96), and 2.01 (95% CI 1.22–3.31) for more than 10 lifetime sessions ( P trend 0.01 with cumulative use). The association was stronger for earlier age at first use ( P trend 0.02). The association was also stronger for melanoma diagnosed when aged 18–29 years (OR for more than 10 lifetime sessions = 6.57, 95% CI 1.41–30.49) than for melanoma diagnosed when 30–39 years (OR 1.60, 95% CI 0.92–2.77 P interaction 0.01). Among those who had ever used a sunbed and were diagnosed between 18 and 29 years of age, three quarters (76%) of melanomas were attributable to sunbed use. Sunbed use is associated with increased risk of early‐onset melanoma, with risk increasing with greater use, an earlier age at first use and for earlier onset disease.
Publisher: Wiley
Date: 30-01-2012
DOI: 10.1002/IJC.27357
Publisher: Springer Science and Business Media LLC
Date: 14-01-2019
DOI: 10.1038/S41467-018-08078-W
Abstract: The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
Publisher: MDPI AG
Date: 11-05-2023
Abstract: MDM2-SNP309 (rs2279744), a common genetic modifier of cancer incidence in Li-Fraumeni syndrome, modifies risk, age of onset, or prognosis in a variety of cancers. Melanoma incidence and outcomes vary by sex, and although SNP309 exerts an effect on the estrogen receptor, no consensus exists on its effect on melanoma. MDM2 and MDM4 restrain p53-mediated tumor suppression, independently or together. We investigated SNP309, an a priori MDM4-rs4245739, and two coinherited variants, in a population-based cohort of 3663 primary incident melanomas. Per-allele and per-haplotype (MDM2_SNP309-SNP285 MDM4_rs4245739-rs1563828) odds ratios (OR) for multiple-melanoma were estimated with logistic regression models. Hazard ratios (HR) for melanoma death were estimated with Cox proportional hazards models. In analyses adjusted for covariates, females carrying MDM4-rs4245739*C were more likely to develop multiple melanomas (ORper-allele = 1.25, 95% CI 1.03–1.51, and Ptrend = 0.03), while MDM2-rs2279744*G was inversely associated with melanoma-death (HRper-allele = 0.63, 95% CI 0.42–0.95, and Ptrend = 0.03). We identified 16 coinherited expression quantitative loci that control the expression of MDM2, MDM4, and other genes in the skin, brain, and lungs. Our results suggest that MDM4/MDM2 variants are associated with the development of subsequent primaries and with the death of melanoma in a sex-dependent manner. Further investigations of the complex MDM2/MDM4 motif, and its contribution to the tumor microenvironment and observed associations, are warranted.
Publisher: Oxford University Press (OUP)
Date: 31-08-2018
DOI: 10.1093/HMG/DDY282
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-12-2016
Abstract: People with a history of melanoma commonly report a fear of cancer recurrence (FCR), yet psychologic support is not routinely offered as part of ongoing melanoma care. This randomized controlled trial examined the efficacy of a psychoeducational intervention to reduce FCR and improve psychologic adjustment in this patient group compared with usual care. The intervention comprised a newly developed psychoeducational resource and three telephone-based psychotherapeutic sessions over a 1-month period timed in accordance with dermatologic appointments. Participants were randomly assigned to intervention (n = 80) or usual care (n = 84). Assessments were completed at baseline, 1 month, and 6 months after dermatologic appointments. Linear mixed models were used to examine differences between treatment and control groups for patient-reported outcomes, including FCR, anxiety, stress, depression, melanoma-related knowledge, health behaviors, satisfaction with melanoma care, unmet needs, and health-related quality of life. At 6 months, the intervention group reported lower FCR severity, trigger, and distress scores than the control group in the baseline-adjusted models the between-group mean difference was −1.9 for FCR severity (95% CI, −3.1 to −0.7 P = .002), −2.0 for FCR triggers (95% CI, −3.3 to −0.7 P = .003), and −0.7 for FCR distress (95% CI, −1.3 to −0.1 P = .03). The decrease in FCR severity (but not triggers or distress) remained statistically significant after adjustment for other covariates ( P = .04). At 6 months, the intervention group also reported lower stress (−1.6 95% CI, −3.1 to −0.2 P = .03) and improved melanoma-related knowledge (1.7 95% CI, 0.8 to 2.6 P .001) compared with the control group. No differences were found between groups for other secondary outcomes. This newly developed evidence-based psychoeducational intervention was effective in reducing FCR and stress and increasing melanoma-related knowledge in people at high risk for another melanoma.
Publisher: Oxford University Press (OUP)
Date: 31-03-2022
DOI: 10.1111/BJD.20956
Abstract: Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS-based risk prediction, particularly assessment of calibration (comparing predicted to observed risks). To evaluate PRS-based melanoma risk prediction in prospective UK and Australian cohorts with European ancestry. We analysed invasive melanoma incidence in the UK Biobank (UKB n = 395 647, 1651 cases) and a case-cohort nested within the Melbourne Collaborative Cohort Study (MCCS, Australia n = 4765, 303 cases). Three PRSs were evaluated: 68 single-nucleotide polymorphisms (SNPs) at 54 loci from a 2020 meta-analysis (PRS68), 50 SNPs significant in the 2020 meta-analysis excluding UKB (PRS50) and 45 SNPs at 21 loci known in 2018 (PRS45). Ten-year melanoma risks were calculated from population-level cancer registry data by age group and sex, with and without PRS adjustment. Predicted absolute melanoma risks based on age and sex alone underestimated melanoma incidence in the UKB [ratio of expected/observed cases: E/O = 0·65, 95% confidence interval (CI) 0·62-0·68] and MCCS (E/O = 0·63, 95% CI 0·56-0·72). For UKB, calibration was improved by PRS adjustment, with PRS50-adjusted risks E/O = 0·91, 95% CI 0·87-0·95. The discriminative ability for PRS68- and PRS50-adjusted absolute risks was higher than for risks based on age and sex alone (Δ area under the curve 0·07-0·10, P < 0·0001), and higher than for PRS45-adjusted risks (Δ area under the curve 0·02-0·04, P < 0·001). A PRS derived from a larger, more erse meta-analysis improves risk prediction compared with an earlier PRS, and might help tailor melanoma prevention and early detection strategies to different risk levels. Recalibration of absolute risks may be necessary for application to specific populations.
Publisher: Wiley
Date: 14-01-2014
DOI: 10.1002/PON.3476
Abstract: Newly diagnosed patients with cancer require education about the disease, the available treatments and potential consequences of treatment. Greater understanding of cancer risk has been found to be associated with greater health-related quality of life, improved psychological adjustment and greater health-related behaviours. The aim of this sytematic review was to assess the effectiveness of educational interventions in improving subjective cancer risk perception and to appraise the quality of the studies. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies. Eligible studies were identified via Medline, PsycINFO, AMED, CINAHL and Embase databases. After screening titles and abstracts, two reviewers independently assessed the eligibility of 206 full-text articles. Forty papers were included in the review the majority of studies were conducted among breast cancer patients (n = 29) and evaluated the effect of genetic counselling on personal perceived risk (n = 25). Pooled results from RCTs (n = 12) showed that, both in the short and long term, educational interventions did not significantly influence risk perception level (standardised mean difference 0.05, 95% CI -0.24-0.34 p = 0.74) or accuracy (odds ratio = 1.96, 95% CI: 0.61-6.25 p = 0.26). Only one RCT reported a short-term difference in risk ratings (p = 0.01). Of prospective observational studies (n = 28), many did demonstrate changes in the level of perceived risk and improved risk accuracy and risk ratings in both the short and long term. However, only one (of three) observational studies reported a short-term difference in risk ratings (p < = 0.003). Further development and investigation of educational interventions using good quality, RCTs are warranted.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2021
DOI: 10.1186/S12889-021-10424-5
Abstract: In iduals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. In iduals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, in iduals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.
Publisher: Oxford University Press (OUP)
Date: 31-10-2015
Publisher: Bioscientifica
Date: 06-2008
DOI: 10.1677/ERC-07-0064
Publisher: Oxford University Press (OUP)
Date: 19-02-2015
DOI: 10.1093/HER/CYV002
Abstract: Melanoma is the most common cancer among 15- to 29-year-olds in Australia, with rates increasing with age. The 'Dark Side of Tanning' (DSOT) mass media c aign was developed in 2007 to influence attitudes related to tanning. This study aimed to assess recall and impact of the DSOT c aign. Data were collected using online surveys of 13- to 44-year-olds living in New South Wales in the summer months of 2007-2010 (n = 7490). Regression models were used to determine predictors of recall of DSOT and to investigate associations between exposure to the c aign and tanning attitudes. The c aign achieved consistently high recall (unprompted recall 42-53% during c aign periods prompted recall 76-84%). Those who recalled DSOT advertisements had a higher likelihood of reporting negative tanning attitudes compared with those who reported no recall, after adjusting for other factors (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.01-1.27 for unprompted recall OR 1.19, 95% CI 1.03-1.36 for prompted recall). Being interviewed in later c aign years was also a significant predictor of negative tanning attitudes (e.g. fourth year of c aign versus first year: OR 1.24, 95% CI 1.01-1.53). These results suggest that mass media c aigns have potential to influence tanning-related attitudes and could play an important role in skin cancer prevention.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Wiley
Date: 11-05-2021
DOI: 10.1111/HEX.13267
Abstract: There is mounting evidence of the benefit of risk‐stratified (risk‐tailored) cancer population screening, when compared to standard approaches. However, shifting towards this approach involves changes to practice that may give rise to implementation challenges. To explore the public's potential acceptance of risk‐stratified screening across different cancer types, including reducing screening frequency if at low risk and the use of personal risk information, to inform implementation strategies. Semi‐structured interviews were conducted with 40 public participants half had received personal genomic risk information and half had not. Participants were prompted to consider different cancers. Data were analysed thematically as one dataset. Themes included the following: (a) a sense of security (b) tailored screening is common sense (c) risk and the need to take action (d) not every cancer is the same and (e) trust and belief in health messages. Both groups expressed similar views. Participants were broadly supportive of risk‐stratified screening across different cancer types, with strong support for increased screening frequency for high‐risk groups. They were less supportive of reduced screening frequency or no screening for low‐risk groups. Findings suggest the public will be amenable to reducing screening when the test is invasive and uncomfortable be less opposed to forgo screening if offered the opportunity to screen at some stage and view visible cancers such as melanoma differently. Approaching distinct cancer types differently, tailoring messages for different audiences and understanding reasons for participating in screening may assist with designing future implementation strategies for risk‐stratified cancer screening.
Publisher: Cold Spring Harbor Laboratory
Date: 20-04-2020
DOI: 10.1101/2020.04.13.20064246
Abstract: The Melanoma Genomics Managing Your Risk Study is a randomised controlled trial that aims to evaluate the efficacy of providing information on personal genomic risk of melanoma in reducing ultraviolet radiation (UV) exposure, stratified by traditional risk group (low or high phenotypic risk) in the general population. The primary outcome is objectively measured total daily Standard Erythemal Doses at 12 months. Secondary outcomes include UV exposure at specific time periods, self-reported sun protection and skin-examination behaviors, psychosocial outcomes, and ethical considerations surrounding offering genomic testing at a population level. A within-trial and modelled economic evaluation will be undertaken from an Australian health system perspective to assess the cost-effectiveness of the intervention. To publish the pre-determined statistical analysis plan (SAP) before database lock and the start of analysis. This SAP describes the data synthesis, analysis principles and statistical procedures for analysing the outcomes from this trial. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid potential analysis bias that may arise from knowledge of the outcome data. This SAP is consistent with best practice and will enable transparent reporting. This SAP has been developed for the Melanoma Genomics Managing Your Risk Study and will be followed to ensure high-quality standards of internal validity and to minimise analysis bias. Prospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12617000691347 (date registered: 15/05/2017).
Publisher: Wiley
Date: 05-03-2018
DOI: 10.1002/IJC.31334
Abstract: Melanoma is the deadliest form of skin cancer, mainly affecting populations of European ancestry. Some observational studies suggest that particular diets reduce melanoma risk, putatively through an increase in polyunsaturated fatty acid (PUFA) consumption. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To date, a randomized controlled trial has not been carried out to examine the relationship between PUFAs and melanoma. Hence, we performed a Mendelian randomisation (MR) study to evaluate the link between PUFAs and melanoma. To perform MR, we used summary results from the largest risk genome-wide association study (GWAS) meta-analysis of melanoma, consisting of 12,874 cases and 23,203 controls. As instrumental variables we selected SNPs associated with PUFA levels from a GWAS meta-analysis of PUFA levels, from the CHARGE consortium. We used the inverse variance weighted method to estimate a causal odds ratio. To aid interpretation, we established a benchmark "large" predicted change in PUFAs in which, for ex le, an increase in docosahexaenoic acid (DPA) of 0.17 units (equal to 1 standard deviation) moves a person from the 17
Publisher: Elsevier BV
Date: 03-2009
Publisher: Elsevier BV
Date: 08-2019
Publisher: American Medical Association (AMA)
Date: 08-2019
Publisher: Springer Science and Business Media LLC
Date: 03-08-2015
DOI: 10.1038/NG.3373
Publisher: American Association for Cancer Research (AACR)
Date: 30-09-2014
DOI: 10.1158/1055-9965.EPI-14-0431
Abstract: Background: We previously reported a significant association between higher UV radiation exposure before diagnosis and greater survival with melanoma in a population-based study in Connecticut. We sought to evaluate the hypothesis that sun exposure before diagnosis was associated with greater survival in a larger, international population-based study with more detailed exposure information. Methods: We conducted a multicenter, international population-based study in four countries—Australia, Italy, Canada, and the United States—with 3,578 cases of melanoma with an average of 7.4 years of follow-up. Measures of sun exposure included sunburn, intermittent exposure, hours of holiday sun exposure, hours of water-related outdoor activities, ambient ultraviolet B (280–320 nm) dose, histologic solar elastosis, and season of diagnosis. Results: Results were not strongly supportive of the earlier hypothesis. Having had any sunburn in 1 year within 10 years of diagnosis was inversely associated with survival solar elastosis—a measure of lifetime cumulative exposure—was not. In addition, none of the intermittent exposure measures—water-related activities and sunny holidays—were associated with melanoma-specific survival. Estimated ambient UVB dose was not associated with survival. Conclusion: Although there was an apparent protective effect of sunburns within 10 years of diagnosis, there was only weak evidence in this large, international, population-based study of melanoma that sun exposure before diagnosis is associated with greater melanoma-specific survival. Impact: This study adds to the evidence that sun exposure before melanoma diagnosis has little effect on survival with melanoma. Cancer Epidemiol Biomarkers Prev 23(10) 2145–52. ©2014 AACR.
Publisher: The Sax Institute
Date: 2019
DOI: 10.17061/PHRP2921910
Abstract: While Australia now has well-established national screening programs for breast, bowel and cervical cancers, research continues into the feasibility of developing systematic screening programs for a number of other cancers. In this paper, experts in their fields provide perspectives on the current state of play and future directions for screening and surveillance for melanoma, Lynch syndrome, and liver, lung and prostate cancers in Australia. Although the evidence does not support population screening, there may be opportunities to prevent thousands of deaths through systematic approaches to the early detection of lung cancer and melanoma, testing for Lynch syndrome, and organised surveillance for hepatocellular carcinoma among in iduals at high risk - guided by targeted research. The paper also looks at what impact new prostate specific antigen testing guidelines are having on screening for prostate cancer.
Publisher: Oxford University Press (OUP)
Date: 24-05-2018
Abstract: Personalized risk assessments using prediction models that incorporate several melanoma risk factors may promote melanoma-prevention behaviours. To evaluate the effect on short-term melanoma-prevention behaviours of web-based, real-time, model-generated personalized melanoma risk information and tailored prevention advice, and its feasibility and clinician acceptability. Between February and April 2016, in an open randomized controlled trial across four general medical practices in New South Wales, Australia, 272 patients were randomly allocated to receive (i) real-time model-generated personalized melanoma risk assessment and tailored melanoma-prevention advice or (ii) generic melanoma-prevention advice. We measured self-reported melanoma-prevention behaviours at baseline and 6 weeks and the intervention's feasibility and acceptability. Follow-up questionnaires were completed by 185 patients at 6 weeks: 174 assessed as average risk and 11 as high or very high risk. There were no statistically significant differences between intervention and control patients in sun protection, sun exposure or early diagnosis behaviours. When stratified by melanoma risk, average risk patients in the intervention group appeared to show greater sun protection at 6 weeks (mean difference = 0.23, on a scale of 1-5 95% confidence interval: 0.01 to 0.45 P = 0.04) than patients in the control group the P value for interaction between intervention and risk category was 0.10. There was favourable feedback from patients and general practitioners. Web-based delivery in general practice of real-time, model-generated personalized melanoma risk prediction and tailored melanoma-prevention advice is feasible and acceptable. An apparent increase in sun protection behaviour in average risk patients warrants further evaluation in different risk groups.
Publisher: Oxford University Press (OUP)
Date: 22-12-2023
DOI: 10.1093/BJD/LJAC111
Publisher: Royal College of General Practitioners
Date: 15-04-2020
DOI: 10.3399/BJGPOPEN20X101028
Abstract: In Australia, melanoma is managed in primary and secondary care settings. An in idual concerned about a suspicious lesion typically presents first to their GP. To identify factors influencing GPs’ decisions to diagnose, treat, or refer patients with suspected melanoma. Semi-structured interviews were undertaken with 23 GPs working in general practice or skin cancer clinics in Australia. The semi-structured interviews were audio-recorded, de-identified, and professionally transcribed. Thematic analysis was used to analyse the data. Considerable variation existed in GPs’ self-reported confidence and involvement in melanoma management. Multiple factors were identified as influencing GPs’ decisions to diagnose, treat, or refer patients with suspected or confirmed melanoma. Health system level factors included the overlapping roles of GPs and specialists, and access to and/or availability of specialists. Practice level factors included opportunities for formal and informal training, and having a GP with a special interest in skin cancer within their practice. GP and patient level factors included the GP’s clinical interests, the clinical features (for ex le, site and size) and histopathology of the suspected melanoma, eligibility for possible sentinel lymph node biopsy, and patient preferences. For some GPs, concerns over misdiagnosis and the option of referring patients at any stage in the melanoma management continuum appeared to affect their interest and confidence in melanoma management. GP involvement in melanoma patient care can extend well beyond cancer screening, prevention and supportive care roles to include provision of definitive melanoma patient management. GPs with an interest in being involved in melanoma management should be encouraged and supported to develop the skills needed to manage these patients, and to refer when appropriate.
Publisher: Springer Science and Business Media LLC
Date: 12-2018
DOI: 10.1039/C7PP00411G
Abstract: Melanoma rates have increased in populations that are mainly European. The main etiologic factor is ultraviolet radiation, from the sun as well as artificial tanning devices. Host factors such as skin color, number of nevi, hair and eye color and tanning ability are critical factors in modifying an in idual's response to the sun. Genetic factors interact with host factors and environmental factors to increase risk. This review summarizes our current knowledge of environment and genetics on melanoma risk and on gene-environment interaction.
Publisher: Oxford University Press (OUP)
Date: 17-09-2011
DOI: 10.1093/HMG/DDR415
Publisher: Oxford University Press (OUP)
Date: 19-02-2020
DOI: 10.1111/BJD.18881
Publisher: Wiley
Date: 10-04-2007
DOI: 10.1002/IJC.22578
Abstract: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, to examine the associations between prediagnostic serum concentrations of C-peptide, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-2, and endometrial cancer risk. Among pre- and post-menopausal women, who were not currently using exogenous hormones, 286 women developed incident endometrial cancer during an average 5.1 years follow-up. Using risk set s ling, 555 matched control subjects were selected. In conditional logistic regression models adjusted for matching factors only, endometrial cancer risk increased with increasing serum levels of C-peptide (relative risks (RR) for the top vs. bottom quartile = 2.13 [95% confidence interval (CI) 1.33-3.41], p(trend) = 0.001, and decreasing serum levels of IGFBP-2 (RR for the top vs. bottom quartile = 0.56 [95% CI 0.35-0.90], p(trend) = 0.03, but was not significantly associated with IGFBP-1 levels (RR for the top vs. bottom quartile = 0.76 [95% CI 0.47-1.21], p(trend) = 0.25). In BMI-adjusted models, only the C-peptide association remained marginally statistically significant (RR for the top vs. bottom quartile = 1.56 [95% CI 0.94-2.57], p(trend) = 0.05 for C-peptide 0.84 [95% CI 0.50-1.40], p(trend) = 0.74 for IGFBP-2 and 1.08 [95% CI 0.65-1.78], p(trend) = 0.86 for IGFBP-1 levels). These associations were stronger among nonfasting women (< or =< or =6 hr since last meal 63% of subjects) but were not evident among fasting women, although the interactions were not statistically significant. The C-peptide-risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women (RR for the top vs. bottom quartile = 1.28 [95% CI 0.67-2.45], p(trend) = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer.
Publisher: Oxford University Press (OUP)
Date: 27-11-2020
DOI: 10.1111/BJD.18524
Publisher: Oxford University Press (OUP)
Date: 05-03-2023
DOI: 10.1093/BJD/LJAD041
Abstract: Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored. To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K– in iduals. Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ in iduals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/– cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank). The cohort comprised 1165 MITF E318K– and 322 E318K+ in iduals. In E318K– cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P & 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P & 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67–2.49) P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54–1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20–1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P & 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ in iduals. RHC alleles/genotypes modify melanoma risk differently in MITF E318K– and E318K+ in iduals. Specifically, although all RHC alleles increase risk relative to wt in E318K– in iduals, only MC1R R increases melanoma risk in E318K+ in iduals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ in iduals.
Publisher: Wiley
Date: 18-05-2007
DOI: 10.1002/IJC.22697
Abstract: Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR=1.56, 95% CI=1.16-2.09, p(trend)<0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR=1.37, 95% CI=1.00-1.88, p(trend)=0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR=1.67, 95% CI=1.14-2.46, p(trend)<0.01) than in the rectum (OR=1.42, 95% CI=0.90-2.25, p(trend)=0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk.
Publisher: Massachusetts Medical Society
Date: 16-09-2004
Publisher: Oxford University Press (OUP)
Date: 12-11-2021
DOI: 10.1111/BJD.19619
Publisher: American Medical Association (AMA)
Date: 02-2015
DOI: 10.1001/JAMADERMATOL.2014.1952
Abstract: Regular surveillance of in iduals at high risk for cutaneous melanoma improves early detection and reduces unnecessary excisions however, a cost analysis of this specialized service has not been undertaken. To determine the mean cost per patient of surveillance in a high-risk clinic from the health service and societal perspectives. We used a bottom-up microcosting method to measure resource use in a consecutive s le of 102 patients treated in a high-risk hospital-based clinic in Australia during a 12-month period. Surveillance and treatment of melanoma. All surveillance and treatment procedures were identified through direct observation, review of medical records, and interviews with staff and were valued using scheduled fees from the Australian government. Societal costs included transportation and loss of productivity. The mean number of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95% CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI, US $532-$665]) the cost discounted across 20 years was A $11,546 (95% CI, A $10,263-$12,829) (US $7839 [95% CI, US $6969-$8710]). The mean annual societal cost per patient (excluding health system costs) was A $972 (95% CI, A $899-$1045) (US $660 [95% CI, US $611-$710]) the cost discounted across 20 years was A $12,721 (95% CI, A $12,554-$14,463) (US $8637 [95% CI, US $8523-$9820]). Diagnosis of melanoma or nonmelanoma skin cancer and frequent excisions for benign lesions in a relatively small number of patients was responsible for positively skewed health system costs. Microcosting techniques provide an accurate cost estimate for the provision of a specialized service. The high societal cost reflects the time that patients are willing to invest to attend the high-risk clinic. This alternative model of care for a high-risk population has relevance for decision making about health policy.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2011
DOI: 10.1038/NATURE10630
Publisher: Wiley
Date: 25-05-2023
DOI: 10.1111/AJD.14087
Publisher: JMIR Publications Inc.
Date: 30-06-2022
Abstract: he large and growing number of melanoma patients who need long term surveillance increasingly exceeds capacity of the dermatology workforce, particularly outside of metropolitan areas. Digital technologies that enable patients to do skin self-examination and send dermoscopic images of lesions of concern to a dermatologist (mobile teledermoscopy) are one potential solution. If these technologies and the remote delivery of melanoma surveillance are to be incorporated into routine clinical practice, they need to be accepted by clinicians providing melanoma care (e.g., dermatologists and general practitioners (GPs)). o explore perceptions of potential benefits and harms of mobile teledermoscopy, and experiences with this technology, among clinicians participating in a pilot randomised controlled trial (RCT) of patient-led melanoma surveillance. his qualitative study was nested within a pilot RCT conducted at dermatologist- and skin specialist GP-led melanoma clinics in New South Wales, Australia. We conducted semi-structured interviews with 8 of the total 11 clinicians who were involved in the trial: 4 dermatologists (3 provided teledermatology, 2 were treating clinicians), 1 surgical oncologist, and 3 GPs with qualifications in skin cancer screening (the remaining 3 GPs declined interview). Thematic analysis was used to analyse the data with reference to concepts ‘medical overuse’ and ‘high-value care’. linicians identified several potential benefits, including increased access to dermatology services, earlier detection of melanomas, reassurance for patients between scheduled visits, and a reduction in unnecessary clinic visits. However, they also identified some potential concerns around use of the technology and remote monitoring that could result in diagnostic uncertainty. These included poor image quality, difficulty making assessments from a 2D digital image (even if good quality), insufficient clinical history provided, and concern that suspicious lesions may have been missed by the patient. Clinicians thought that uncertainty arising from these concerns, together with perceived potential medico-legal consequences from missing a diagnosis, might lead to increases in unnecessary clinic visits and procedures. Strategies suggested for achieving high-value care included managing clinical uncertainty in order to decrease the potential for medical overuse, and by ensuring optimal placement of patient-led teledermoscopy within existing clinical care pathways to increase the potential for benefits. linicians were enthusiastic about the potential and experienced benefits of mobile teledermoscopy however, managing clinical uncertainty will be necessary to achieve these benefits in clinical care outside of trial contexts, and to minimise potential harms from medical overuse.
Publisher: Wiley
Date: 22-07-2021
DOI: 10.1111/AJD.13670
Publisher: Elsevier BV
Date: 12-2021
Publisher: BMJ
Date: 06-2022
DOI: 10.1136/BMJOPEN-2021-059829
Abstract: Australia has the highest incidence of skin cancer in the world, with two out of three Australians expected to be diagnosed with skin cancer in their lifetime. Such incidence necessitates large-scale, effective skin cancer management practices. General practitioners (in mainstream practice and in skin cancer clinics) play an important role in skin cancer care provision, making decisions based on relevant evidence-based guidelines, protocols, experience and training. Diversity in these decision-making practices can result in unwarranted variation. Quality indicators are frequently implemented in healthcare contexts to measure performance quality at the level of the clinician and healthcare practice and mitigate unwarranted variation. Such measurements can facilitate performance comparisons between peers and a standard benchmark, often resulting in improved processes and outcomes. A standardised set of quality indicators is yet to be developed in the context of primary care skin cancer management. This research aims to identify, develop and generate expert consensus on a core set of quality indicators for skin cancer management in primary care. This mixed-methods study involves (1) a scoping review of the available evidence on quality indicators in skin cancer management in primary care, (2) identification and development of a core set of quality indicators through interviews/qualitative proforma surveys with participants, and (3) a focus group involving discussion of quality indicators according to Nominal Group Technique. Qualitative and quantitative data will be collected and analysed using thematic and descriptive statistical analytical methods. Approval was granted by the university’s Research Ethics Committee (HREC no. 520211051532420). Results from this study will be widely disseminated in publications, study presentations, educational events and reports.
Publisher: Oxford University Press (OUP)
Date: 08-02-2016
DOI: 10.1093/JNCI/DJW004
Publisher: Elsevier BV
Date: 04-2002
Publisher: American Medical Association (AMA)
Date: 10-2017
Publisher: Springer Science and Business Media LLC
Date: 16-12-2020
Publisher: Springer Science and Business Media LLC
Date: 20-11-2014
Publisher: American Medical Association (AMA)
Date: 2018
Publisher: BMJ
Date: 10-2016
DOI: 10.1097/IGC.0000000000000790
Abstract: Physical activity is associated with improved health outcomes for people with cancer. We aimed to identify physical activity correlates, barriers, and preferences among women with gynecological cancer. A self-administered questionnaire was completed by 101 women diagnosed with gynecological cancer (mostly ovarian cancer [59%] and endometrial cancer [23%]) within the previous 2 years, at 2 major hospitals in Sydney, Australia. Physical activity was measured for the past 7 days. Thirteen potential barriers were scored on a 5-point scale. Associations with physical activity were assessed using Spearman correlations ( r s ) and multivariate logistic regression. Factors associated with being sufficiently active (≥150 min/wk physical activity) were being in the follow-up phase of the cancer trajectory (odds ratio [OR], 7.0 95% confidence interval [CI], 1.5 to 33.4 compared with other phases) and prediagnosis physical activity (OR, 4.6 95% CI, 1.1 to 18.5 for the highest vs lowest tertile). The most common barriers were “too tired” and “not well enough,” and both were associated with lower physical activity ( r s , −0.20 and −0.22, respectively). The odds of having disease-specific barriers was higher for women with ovarian cancer (OR, 4.6 P = 0.04) and women receiving chemotherapy or radiation therapy (OR, 8.3 P = 0.008). “Lack of interest” ( r s , −0.26) and “never been active” ( r s, −0.23) were also inversely correlated with physical activity, although less common. Forty-three percent of women indicated that they were extremely or very interested to have a one-to-one session with an exercise physiologist. Participants’ preferred time of starting a physical activity program was 3 to 6 months after treatment (26%) or during treatment (23%). Walking was the preferred type of physical activity. Strategies to increase physical activity among women with gynecological cancer should include a focus on reducing disease-specific barriers and target women who have done little physical activity in the past or who are in the treatment phases of care.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-08-2021
Publisher: Elsevier BV
Date: 04-2020
Publisher: Oxford University Press (OUP)
Date: 22-09-2020
DOI: 10.1111/BJD.18411
Publisher: Oxford University Press
Date: 21-12-2017
DOI: 10.1093/OSO/9780190238667.003.0057
Abstract: Melanoma is a cancer of melanocytes, cells that produce the brown-black skin pigment melanin. Melanocytes originate in cells of the neural crest and migrate during embryogenesis, principally to the epidermis, eyes, and some mucous membranes (mouth, nose, esophagus, anus, genitourinary organs, and conjunctiva). Cutaneous melanoma afflicts mainly fair-skinned people of European origin, among whom sun exposure is the major cause. Five-year relative survival can exceed 90%. Invasive cutaneous melanoma in US whites occurs mostly on the trunk (34%), and upper limbs and shoulders (26%). Melanoma incidence rates have been increasing predominantly in European-origin populations. Ultraviolet (UV) radiation, from the sun or artificial tanning devices, probably both initiates and promotes melanoma. Nevi are markers of increased melanoma risk and direct precursors in some cases nevus-prone people may require only modest sun exposure to initiate melanoma. Other risk factors include family history and sun sensitivity.
Publisher: Oxford University Press (OUP)
Date: 10-08-2023
DOI: 10.1093/BJD/LJAD275
Abstract: People with a previous melanoma are at increased risk of developing another primary melanoma when compared with the general population. Understanding risk factors associated with multiple primary melanomas can inform patient education and tailored surveillance. We conducted a systematic review and meta-analysis to examine risk factors for subsequent primary melanoma. A systematic literature search was conducted on CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and MEDLINE. Studies reporting a risk estimate or raw frequencies and conducted between 1982 and August 2022 were included. Adjusted risk estimates were prioritised over univariable risk estimates. PRISMA reporting guidelines were followed. Random effects meta-analysis was conducted to derive pooled estimates. Quality assessment was conducted by two researchers using the Newcastle-Ottawa scale. GRADE was used to rate certainty and quality of evidence. Data from 27 studies involving 388,424 participants were pooled and analysed. Risk factors assessed included age and gender, environmental, lifestyle, phenotypic, genetic, and histopathological factors, and there was wide variation in how they were categorised and analysed. Independent risk factors identified from pooled analyses included male gender (HR 1.46, 95% confidence interval (CI) 1.40-1.53), increasing age per 10-years (HR 1.19, 95% CI 1.14-1.24), light skin colour (HR 1.44, 95% CI 1.23-1.70), family history (OR 1.79, 95% CI 1.25-2.56), CDKN2A mutation (OR 5.29, 95% CI 2.70-10.37), high or moderate nevus count (OR 2.63, 95% CI 1.61-4.30) and (OR 1.64, 95% CI 1.07-2.51) respectively, one or more atypical nevi (OR 3.01, 95% CI 1.52-5.97), first lesions occurring on the head/neck, lentigo maligna subtype (HR 1.16, 95% CI 1.15-1.17), other subtype (HR 1.14, 95% CI 1.03-1.27), and inadequate sun protection (HR 1.85, 95% CI 0.98-3.50). Based on GRADE criteria, there was high to very low confidence in the pooled effect estimates. This meta-analysis identified several consistent, independent risk factors for the development of subsequent primary melanoma. These findings can assist in stratifying risk of subsequent melanoma, tailoring skin check schedules and informing patient education. PROSPERO registration number - CRD42020191255.
Publisher: Springer Science and Business Media LLC
Date: 30-06-2020
DOI: 10.1186/S13063-020-04351-W
Abstract: The Melanoma Genomics Managing Your Risk Study is a randomised controlled trial that aims to evaluate the efficacy of providing information on personal genomic risk of melanoma in reducing ultraviolet radiation (UV) exposure, stratified by traditional risk group (low or high phenotypic risk) in the general population. The primary outcome is objectively measured total daily Standard Erythemal Doses at 12 months. Secondary outcomes include UV exposure at specific time periods, self-reported sun protection and skin-examination behaviours, psychosocial outcomes, and ethical considerations surrounding offering genomic testing at a population level. A within-trial and modelled economic evaluation will be undertaken from an Australian health system perspective to assess the cost-effectiveness of the intervention. To publish the pre-determined statistical analysis plan (SAP) before database lock and the start of analysis. This SAP describes the data synthesis, analysis principles and statistical procedures for analysing the outcomes from this trial. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid potential analysis bias that may arise from knowledge of the outcome data. This SAP is consistent with best practice and should enable transparent reporting. This SAP has been developed for the Melanoma Genomics Managing Your Risk Study and will be followed to ensure high-quality standards of internal validity and to minimise analysis bias. Prospectively registered with the Australian New Zealand Clinical Trials Registry, ID: ACTR N12617000691347 . Registered on 15 May 2017.
Publisher: Springer Science and Business Media LLC
Date: 29-06-2020
DOI: 10.1186/S12889-020-09143-0
Abstract: Genomic risk information, based on common genomic susceptibility variants associated with risk of complex diseases such as cancer, may be incorporated into personalised prevention and screening strategies. We aimed to engage with members of the public, who are important stakeholders in this process, to further inform program development and other implementation outcomes such as acceptability and appropriateness. Semi-structured interviews were undertaken with 30 participants (aged 24–69 years, 50% female) recruited from a pilot trial in which they received personalised genomic risk information for melanoma. We explored participants’ views and attitudes towards offering general personal genomic risk information to the broader population. The data were analysed thematically. Two overarching themes relevant to implementation considerations were identified. Firstly, participants’ preferences for accepting an offer of genomic risk information were based on family history, disease incidence and the possibility of prevention. Secondly, participants felt that the processes for offering risk information should be based on in idual preferences, triaged according to risk and be supported by a health professional trained in genomics. Participants felt that offering personal genomic risk information to the general population to inform prevention and early detection recommendations is acceptable, particularly for common, complex conditions such as cancer. Understanding participants’ preferences for receiving genomic risk information will assist with communication strategies and health workforce planning. We anticipate that these findings will contribute to the development of implementation strategies for incorporating genomic risk information into routine clinical practice.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.ZEFQ.2017.05.011
Abstract: Shared decision making (SDM) is now firmly established within national clinical standards for accrediting hospitals, day procedure services, public dental services and medical education in Australia, with plans to align general practice, aged care and disability service. Implementation of these standards and training of health professionals is a key challenge for the Australian health sector at this time. Consumer involvement in health research, policy and clinical service governance has also increased, with a major focus on encouraging patients to ask questions during their clinical care. Tools to support shared decision making are increasingly used but there is a need for more systemic approaches to their development, cultural adaptation and implementation. Sustainable solutions to ensure tools are kept up-to-date with the best available evidence will be important for the future.
Publisher: Oxford University Press (OUP)
Date: 10-04-2021
DOI: 10.1093/JNCI/DJAB076
Abstract: Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older in iduals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest. We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12 712 in iduals in the ASPirin in Reducing Events in the Elderly Trial. We evaluated incident melanomas diagnosed during the trial and prevalent melanomas diagnosed preenrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per SD) and categorical (low-risk [0%-20%], medium-risk [21%-80%], high-risk [81%-100%] groups) with incident melanoma. Logistic regression examined the association between PRS and prevalent melanoma. At baseline, mean participant age was 75 years 55.0% were female, and 528 (4.2%) had prevalent melanomas. During follow-up (median = 4.7 years), 120 (1.0%) incident cutaneous melanomas occurred, 98 of which were in participants with no history. PRS was associated with incident melanoma (hazard ratio = 1.46 per SD, 95% confidence interval [CI] = 1.20 to 1.77) and prevalent melanoma (odds ratio [OR] = 1.55 per SD, 95% CI = 1.42 to 1.69). Participants in the highest-risk PRS group had increased risk compared with the low-risk group for incident melanoma (OR = 2.51, 95% CI = 1.28 to 4.92) and prevalent melanoma (OR = 3.66, 95% CI = 2.69 to 5.05). When stratifying by sex, only males had an association between the PRS and incident melanoma, whereas both sexes had an association between the PRS and prevalent melanoma. A genomic risk score is associated with melanoma risk in older in iduals and may contribute to targeted surveillance.
Publisher: Oxford University Press (OUP)
Date: 06-10-2017
DOI: 10.1111/BJD.15784
Publisher: Wiley
Date: 30-01-2014
DOI: 10.1111/PCMR.12215
Publisher: Wiley
Date: 24-06-2023
DOI: 10.1111/AJD.14113
Publisher: Elsevier BV
Date: 05-2021
Publisher: Oxford University Press (OUP)
Date: 20-07-2017
DOI: 10.1111/BJD.15744
Abstract: Receiving information about genomic risk of melanoma might trigger conversations about skin cancer prevention and skin examinations. To explore conversations prompted by receiving personalized genomic risk of melanoma with family, friends and health professionals. We used a mixed-methods approach. Participants without a personal history and unselected for a family history of melanoma (n = 103, aged 21-69 years, 53% women) completed questionnaires 3 months after receiving a personalized melanoma genomic risk assessment. Semistructured interviews were undertaken with 30 participants in high, average and low genomic risk categories, and data were analysed thematically. From the questionnaires, 74% of participants communicated their genomic risk information with family, and 49% with friends. Communication with a health professional differed by risk level: 41%, 16% and 12% for high, average and low risk, respectively (P = 0·01). Qualitative analysis showed that perceived 'shared risk' and perceived interest of family and friends were motivations for discussing risk or prevention behaviours. The information prompted conversations with family and health professionals about sun protection and skin checks, and general conversations about melanoma risk with friends. Reasons for not discussing with family included existing personal or family health concerns, or existing high levels of sun protection behaviour among family members. Personalized melanoma genomic risk information can prompt risk-appropriate discussions about skin cancer prevention and skin examinations with family and health professionals. Sharing this information with others might increase its impact on melanoma prevention and skin examination behaviours, and this process could be used to encourage healthy behaviour change within families.
Publisher: JMIR Publications Inc.
Date: 07-2022
DOI: 10.2196/35916
Abstract: Current clinician-led melanoma surveillance models require frequent routinely scheduled clinic visits, with associated travel, cost, and time burden for patients. Patient-led surveillance is a new model of follow-up care that could reduce health care use such as clinic visits and medical procedures and their associated costs, increase access to care, and promote early diagnosis of a subsequent new melanoma after treatment of a primary melanoma. Understanding patient experiences may allow improvements in implementation. This study aims to explore patients’ experiences and perceptions of patient-led surveillance during the 6 months of participation in the MEL-SELF pilot randomized controlled trial. Patient-led surveillance comprised regular skin self-examination, use of a mobile dermatoscope to image lesions of concern, and a smartphone app to track and send images to a teledermatologist for review, in addition to usual care. Semistructured interviews were conducted with patients previously treated for melanoma localized to the skin in New South Wales, Australia, who were randomized to the patient-led surveillance (intervention group) in the trial. Thematic analysis was used to analyze the data with reference to the technology acceptance model. We interviewed 20 patients (n=8, 40% women and n=12, 60% men median age 62 years). Patients who were more adherent experienced benefits such as increased awareness of their skin and improved skin self-examination practice, early detection of melanomas, and opportunities to be proactive in managing their clinical follow-up. Most participants experienced difficulty in obtaining clear images and technical problems with the app. These barriers were overcome or persevered by participants with previous experience with digital technology and with effective help from a skin check partner (such as a spouse, sibling, or friend). Having too many or too few moles decreased perceived usefulness. Patients with melanoma are receptive to and experience benefits from patient-led surveillance using teledermoscopy. Increased provision of training and technical support to patients and their skin check partners may help to realize the full potential benefits of this new model of melanoma surveillance.
Publisher: American Medical Association (AMA)
Date: 12-2014
Publisher: Oxford University Press (OUP)
Date: 18-02-2021
DOI: 10.1111/BJD.19705
Abstract: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA s les. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.
Publisher: American Medical Association (AMA)
Date: 04-2014
DOI: 10.1001/JAMADERMATOL.2013.8890
Abstract: Currently, there is no comprehensive assessment of melanoma risk prediction models. To systematically review published studies reporting multivariable risk prediction models for incident primary cutaneous melanoma for adults. EMBASE, MEDLINE, PREMEDLINE, and Cochrane databases were searched to April 30, 2013. Eligible studies were hand searched and citation tracked. Two independent reviewers extracted information. Nineteen studies reporting 28 melanoma prediction models were included. The number of predictors in the final models ranged from 2 to 13 the most common were nevi, skin type, freckle density, age, hair color, and sunburn history. There was limited reporting and substantial variation among the studies in model development and performance. Discrimination (the ability of the model to differentiate between patients with and without melanoma) was reported in 9 studies and ranged from fair to very good (area under the receiver operating characteristic curve, 0.62-0.86). Few studies assessed internal or external validity of the models or their use in clinical and public health practice. Of the published melanoma risk prediction models, the risk prediction tool developed by Fears and colleagues, which was designed for the US population, appears to be the most clinically useful and may also assist in identifying high-risk groups for melanoma prevention strategies. Few melanoma risk prediction models have been comprehensively developed and assessed. More external validation and prospective evaluation will help translate melanoma risk prediction models into useful tools for clinical and public health practice.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Oxford University Press (OUP)
Date: 02-2021
DOI: 10.1111/BJD.19706
Publisher: BMJ
Date: 20-05-2021
DOI: 10.1136/MEDETHICS-2019-105934
Abstract: Publics are key stakeholders in population genomic screening and their perspectives on ethical considerations are relevant to programme design and policy making. Using semi-structured interviews, we explored social views and attitudes towards possible future provision of personalised genomic risk information to populations to inform prevention and/or early detection of relevant conditions. Participants were members of the public (n=30) who had received information on their personal genomic risk of melanoma as part of a research project. The focus of the analysis presented here is participants’ views regarding ethical considerations relevant to population genomic screening more generally. Data were analysed thematically and four key themes related to ethical considerations were identified: (i) personal responsibility for health: ‘forewarned is forearmed’ (ii) perceptions of, and responses to, genetic fatalism (iii) implications for parenting and reproduction (iv) ided views on choosing to receive genomic risk information. Ethical considerations underlying these themes include the valorisation of information and choice, paternalism, non-directiveness and increasing responsibilisation of in iduals in health and healthcare. These findings arguably indicate a thin public conceptualisation of population genomic testing, which draws heavily on how these themes tend to be described in existing social discourses. Findings suggest that further public engagement is required to increase complexity of debate, to consider (for ex le) the appropriate place of in idual and social interests in population genomic testing. Further discernment of relevant ethical approaches, drawing on ethical frameworks from both public health and clinical settings, will also assist in determining the appropriate implementation of population genomic screening for complex conditions.
Publisher: Springer Science and Business Media LLC
Date: 08-01-2007
DOI: 10.1007/S10552-006-0094-7
Abstract: To (1) determine the nature of the association between physical activity and endometrial cancer risk (2) assess the contribution of variation in the quality of physical activity measurement to inconsistencies in study results and (3) review the biologic mechanisms that might mediate possible effects of physical activity on risk. We reviewed and summarized all published epidemiologic studies examining physical activity and endometrial cancer risk, and evidence relating to possible biologic mechanisms. We assigned each study a quality score for physical activity measurement. Fourteen of the 18 studies showed a convincing or possible protective effect of physical activity on endometrial cancer risk, with an average relative risk reduction of around 30%. A dose-response relation was observed in 7 of 13 studies. The quality score was not related to the observed strength of association or the presence of a dose-response relation. There was epidemiologic and biologic evidence that vigorous activity, as well as light and moderate intensity activities, such as housework, gardening or walking for transportation, may reduce risk. Physical activity probably has a protective role in endometrial cancer development. More epidemiologic and biologic evidence is needed to make conclusive recommendations on optimal types, characteristics or time periods of physical activity.
Publisher: Springer Science and Business Media LLC
Date: 11-2009
DOI: 10.1038/EJCN.2009.74
Abstract: To describe dietary carbohydrate intakes and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Between 1995 and 2000, 36 034 subjects, aged between 35-74 years, were administered a standardized, 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes (g/day) of total carbohydrate, sugars, starch and fibre were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. Adjusted mean total carbohydrate intakes were highest in Italy and in the UK health-conscious cohort, and were lowest in Spain, Greece and France. Total fibre intakes were highest in the UK health-conscious cohort and lowest in Sweden and the UK general population. Bread contributed the highest proportion of carbohydrates (mainly starches) in every centre. Fruit consumption contributed a greater proportion of total carbohydrates (mainly sugars) among women than among men, and in southern centres compared with northern centres. Bread, fruits and vegetables represented the largest sources of fibre, but food sources varied considerably between centres. In stratified analyses, carbohydrate intakes tended to be higher among subjects who were physically active, never-smokers or non-drinkers of alcohol. Dietary carbohydrate intakes and in particular their food sources varied considerably between these 10 European countries. Intakes also varied according to gender and lifestyle factors. These data will form the basis for future aetiological analyses of the role of dietary carbohydrates in influencing health and disease.
Publisher: Springer Science and Business Media LLC
Date: 11-2009
DOI: 10.1038/EJCN.2009.81
Abstract: To describe dietary glycaemic index (GI) and glycaemic load (GL) values in the population participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study according to food groups, nutrients and lifestyle characteristics. Single 24-h dietary recalls (24-HDRs) from 33 566 subjects were used to calculate dietary GI and GL, and an ad hoc database was created as the main reference source. Mean GI and GL intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. GI was the lowest in Spain and Germany, and highest in the Netherlands, United Kingdom and Denmark for both genders. In men, GL was the lowest in Spain and Germany and highest in Italy, whereas in women, it was the lowest in Spain and Greece and highest in the UK health-conscious cohort. Bread was the largest contributor to GL in all centres (15-45%), but it also showed the largest inter-in idual variation. GL, but not GI, tended to be lower in the highest body mass index category in both genders. GI was positively correlated with starch and intakes of bread and potatoes, whereas it was correlated negatively with intakes of sugar, fruit and dairy products. GL was positively correlated with all carbohydrate components and intakes of cereals, whereas it was negatively correlated with fat and alcohol and with intakes of wine, with large variations across countries. GI means varied modestly across countries and genders, whereas GL means varied more, but it may possibly act as a surrogate of carbohydrate intake.
Publisher: BMJ
Date: 2004
DOI: 10.1136/FN.89.1.F5
Abstract: Recent evidence suggests that inflammatory cytokines may play an important role in cerebral and pulmonary injury, especially in preterm infants. Immunomodulatory agents may help to limit such injury by reducing inflammation. Immunoglobulin has multiple anti-inflammatory properties and can modulate the inflammatory cytokine response. New evidence is required to test the hypotheses that prophylaxis or treatment with intravenous immunoglobulin may limit such inflammatory damage.
Publisher: Springer International Publishing
Date: 25-11-2015
DOI: 10.1007/978-3-319-22539-5_2
Abstract: The epidemiology of melanoma is complex, and in idual risk depends on sun exposure, host factors, and genetic factors, and in their interactions as well. Sun exposure can be classified as intermittent, chronic, or cumulative (overall) exposure, and each appears to have a different effect on type of melanoma. Other environmental factors, such as chemical exposures-either through occupation, atmosphere, or food-may increase risk for melanoma, and this area warrants further study. Host factors that are well known to be important are the numbers and types of nevi and the skin phenotype. Genetic factors are classified as high-penetrant genes, moderate-risk genes, or low-risk genetic polymorphisms. Subtypes of tumors, such as BRAF-mutated tumors, have different risk factors as well as different therapies. Prevention of melanoma has been attempted using various strategies in specific subpopulations, but to date optimal interventions to reduce incidence have not emerged.
Publisher: Wiley
Date: 30-04-2023
DOI: 10.5694/MJA2.51910
Publisher: Oxford University Press (OUP)
Date: 02-2018
DOI: 10.1111/BJD.16163
Publisher: BMJ
Date: 05-2023
DOI: 10.1136/BMJOPEN-2022-067744
Abstract: Skin cancer is Australia’s most common and costly cancer. We examined the frequency of Australian general practice consultations for skin cancer-related conditions, by patient and general practitioner (GP) characteristics and by time period. Nationally representative, cross-sectional survey of general practice clinical activity. Patients aged 15 years or older having a skin cancer-related condition managed by GPs in the Bettering the Evaluation And Care of Health study between April 2000 and March 2016. Proportions and rates per 1000 encounters. In this period, 15 678 GPs recorded 1 370 826 patient encounters, of which skin cancer-related conditions were managed 65 411 times (rate of 47.72 per 1000 encounters, 95% CI 46.41 to 49.02). Across the whole period, ‘skin conditions’ managed were solar keratosis (29.87%), keratinocyte cancer (24.85%), other skin lesion (12.93%), nevi (10.98%), skin check (10.37%), benign skin neoplasm (8.76%) and melanoma (2.42%). Over time, management rates increased for keratinocyte cancers, skin checks, skin lesions, benign skin neoplasms and melanoma but remained stable for solar keratoses and nevi. Skin cancer-related encounter rates were higher for patients aged 65–89 years, male, living in Queensland or in regional or remote areas, with lower area-based socioeconomic status, of English-speaking background, Veteran card holders and non-healthcare card holders and for GPs who were aged 35–44 years or male. These findings show the spectrum and burden of skin cancer-related conditions managed in general practice in Australia, which can guide GP education, policy and interventions to optimise skin cancer prevention and management.
Publisher: BMJ
Date: 2003
DOI: 10.1136/FN.88.1.F23
Abstract: To compare the survival and short term morbidity of all New Zealand very low birthweight (VLBW) infants born in two epochs, 1986 and 1998-1999. All level III and level II neonatal intensive care units (NICUs) in New Zealand. In 1986, data were prospectively collected for a study of retinopathy of prematurity (ROP). In 1998-1999, prospective data were collected by the Australian and New Zealand Neonatal Network (ANZNN). Both cohorts included all VLBW infants born during the calendar year and admitted to a NICU. Data were collected from birth until discharge home or death. More VLBW infants were admitted for care in 1998-1999 (n = 1084, 0.96% of livebirths) than in 1986 (n = 413, 0.78% of livebirths p < 0.001), including a higher proportion of VLBW infants of < 1000 g birth weight (38% v 32% respectively p < 0.05). Survival to discharge home increased from 81.8% in 1986 to 90.3% in 1998-1999 (p < 0.001). The 1998-1999 cohort had a higher proportion of infants born in a hospital with a level III NICU (87% v 72% in 1986 p < 0.001) and receiving antenatal corticosteroids (80% v 58% in 1986 p < 0.001). In 1998-1999, the incidence of several morbidities had decreased compared with 1986, including oxygen dependency at 28 days (29% v 39% respectively p = 0.001) and at 36 weeks postmenstrual age (16% v 23% p = 0.002), grade 1 intraventricular haemorrhage (IVH) (8% v 24% p < 0.001), grade 2/3 IVH (5% v 11% p < 0.001), and stage 3/4 ROP for infants < 1000 g (6% v 13% p < 0.001). The outlook for VLBW infants in New Zealand has improved since 1986.
Publisher: Wiley
Date: 07-06-2019
DOI: 10.1111/JDV.15680
Publisher: Elsevier BV
Date: 07-2019
Publisher: American Medical Association (AMA)
Date: 05-2021
Publisher: Wiley
Date: 04-1999
DOI: 10.1046/J.1440-1754.1999.00317.X
Abstract: To determine safe and appropriate alarm limits for the Marquette 8000 pulse oximeter to prevent hyperoxic and hypoxic episodes in neonates. It is necessary to define these limits for each brand of oximeter because of the variance in nonuser adjustable calibration algorithms used in pulse oximeters. Oxygen saturation values obtained from a Marquette 8000 pulse oximeter (SpO2) were compared with simultaneous arterial blood gas PaO2 values obtained from blood gas analysis, for 322 s les in 24 consecutive neonates (median 30 weeks' gestation). In order to prevent 95% of hyperoxic episodes (PaO2 > 90 mmHg), the upper alarm limit was 95% SpO2. Similarly, to prevent 95% of hypoxic episodes (PaO2 < 40 mmHg), the lower alarm limit was 95% SpO2. A sensitivity lower than 95% had to be accepted to develop an alarm range which prevented both hyperoxic and hypoxic episodes. To maintain PaO2 values between 40 and 90 mmHg, an appropriate alarm range of 94-97% SpO2 (90% sensitivity, 28% specificity) was established. The relative merits of high sensitivity versus high specificity should be considered when determining appropriate alarm limits. Alarm limits which represent a balance between sensitivity and specificity will minimise false alarms and provide a clinically practical range. It would be useful for this type of information to be available for each brand of oximeter, to assist the user in determining appropriate alarm settings.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2021
DOI: 10.1161/CIRCOUTCOMES.119.005623
Abstract: Mendelian randomization is an epidemiological approach to making causal inferences using observational data. It makes use of the natural randomization that occurs in the generation of an in idual’s genetic makeup in a way that is analogous to the study design of a randomized controlled trial and uses instrumental variable analysis where the genetic variant(s) are the instrument (analogous to random allocation to treatment group in an randomized controlled trial). As with any instrumental variable, there are 3 assumptions that must be made about the genetic instrument: (1) it is associated (not necessarily causally) with the exposure (relevance condition) (2) it is associated with the outcome only through the exposure (exclusion restriction condition) and (3) it does not share a common cause with the outcome (ie, no confounders of the genetic instrument and outcome, independence condition). Using the ex le of type II diabetes and coronary artery disease, we demonstrate how the method may be used to investigate causality and discuss potential benefits and pitfalls. We conclude that although Mendelian randomization studies can usually not establish causality on their own, they may usefully contribute to the evidence base and increase our certainty about the effectiveness (or otherwise) of interventions to reduce cardiovascular disease.
Publisher: MDPI AG
Date: 26-09-2022
DOI: 10.3390/JPM12101581
Abstract: Personalized polygenic risk information may be used to guide risk-based melanoma prevention and early detection at a population scale, but research on communicating this information is limited. This mixed-methods study aimed to assess the acceptability of a genetic counselor (GC) phone call in communicating polygenic risk information in the Melanoma Genomics Managing Your Risk randomized controlled trial. Participants (n = 509) received personalized melanoma polygenic risk information, an educational booklet on melanoma prevention, and a GC phone call, which was audio-recorded. Participants completed the Genetic Counseling Satisfaction Survey 1-month after receiving their risk information (n = 346). A subgroup took part in a qualitative interview post-study completion (n = 20). Survey data were analyzed descriptively using SPSS, and thematic analysis of the qualitative data was conducted using NVivo 12.0 software. The survey showed a high level of acceptability for the GC phone call (mean satisfaction score overall: 4.3 out of 5, standard deviation (SD): 0.6) with differences according to gender (mean score for women: 4.4, SD: 0.6 vs. men: 4.2, SD: 0.7 p = 0.005), health literacy (lower literacy: 4.1, SD: 0.8 average: 4.3, SD: 0.6 higher: 4.4, SD: 0.6: p = 0.02) and polygenic risk group (low risk: 4.5, SD: 0.5, SD: average: 4.3, SD: 0.7, high: 4.3, SD: 0.7 p = 0.03). During the GC phone calls, the discussion predominately related to the impact of past sun exposure on personal melanoma risk. Together our findings point to the importance of further exploring educational and support needs and preferences for communicating personalized melanoma risk among population subgroups, including erse literacy levels.
Publisher: American Medical Association (AMA)
Date: 09-2018
Publisher: Elsevier BV
Date: 12-2018
Publisher: Oxford University Press (OUP)
Date: 04-2020
DOI: 10.1111/BJD.18986
Publisher: Wiley
Date: 18-05-2007
DOI: 10.1002/IJC.22676
Abstract: The etiologic role of physical activity in endometrial cancer risk remains unclear given the few epidemiologic studies that have been conducted. To investigate this relation more fully, an analysis was undertaken in the European prospective investigation into cancer and nutrition (EPIC). During an average 6.6 years of follow-up, 689 incident endometrial cancer cases were identified from an analytic cohort within EPIC of 253,023 women. Cox proportional hazards models were used to estimate the associations between type of activity (total, occupational, household, recreational) and endometrial cancer risk. For total activity, women in the highest compared with the lowest quartile of activity had a risk of 0.88 (95% confidence interval (95% CI=0.61-1.27). No clear associations between each type of activity and endometrial cancer risk were found for the total study population combined. Associations were more evident in the stratified results, with premenopausal women who were active versus inactive experiencing a risk of 0.66 (95% CI=0.38-1.14) overall. Among premenopausal women, for household and recreational activities the risk estimates in the highest as compared with the lowest quartiles were, respectively, 0.48 (95% CI=0.23-0.99) and 0.78 (95% CI=0.44-1.39). No effect modification by body mass index, hormone replacement therapy, oral contraceptive use or energy intake was found. This study provides no evidence of a protective effect of increased physical activity in endometrial cancer risk in all women but some support for a benefit among premenopausal women. The relative risk reductions are most apparent for household activities.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Oxford University Press (OUP)
Date: 05-2017
DOI: 10.1111/BJD.15476
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Publisher: BMJ
Date: 03-06-2008
Abstract: To review (1) the epidemiological literature on physical activity and the risk of breast cancer, examining the effect of the different parameters of activity and effect modification within different population subgroups and (2) the biological mechanisms whereby physical activity may influence the risk of breast cancer. A review of all published literature to September 2007 was conducted using online databases 34 case-control and 28 cohort studies were included. The impact of the different parameters of physical activity on the association between activity and the risk of breast cancer was examined by considering the type of activity performed, the timing of activity over the life course and the intensity of activity. Effect modification of this association by menopausal status, body mass index (BMI), racial group, family history of breast cancer, hormone receptor status, energy intake and parity were also considered. Evidence for a risk reduction associated with increased physical activity was found in 47 (76%) of 62 studies included in this review with an average risk decrease of 25-30%. A dose-response effect existed in 28 of 33 studies. Stronger decreases in risk were observed for recreational activity, lifetime or later life activity, vigorous activity, among postmenopausal women, women with normal BMI, non-white racial groups, those with hormone receptor negative tumours, women without a family history of breast cancer and parous women. The effect of physical activity on the risk of breast cancer is stronger in specific population subgroups and for certain parameters of activity that need to be further explored in future intervention trials.
Publisher: Springer Science and Business Media LLC
Date: 25-05-2017
DOI: 10.1245/S10434-017-5890-7
Abstract: Standardization of the clinical management of melanoma through the formulation of national guidelines, based on interpretation of the existing evidence and consensus expert opinion, seeks to improve quality of care however, adherence to national guidelines has not been well studied. A population-based, cross-sectional study of the clinical management of all patients with newly notified primary melanomas in the state of New South Wales, Australia, during 2006/2007 was conducted using cancer registry identification and questionnaires completed by treating physicians. Surgical margin guidelines were adhered to in 35% of cases 45% were over treated and 21% were undertreated. Factors independently associated with non-concordance on multivariate analysis were lower Breslow thickness, lower socio-economic status of the physician's practice location, older physician age, lower physician caseload, and physicians who biopsied the lesion and then referred for definitive management. Complications were not related to over- or under-treatment on multivariate analysis (p = 0.72). Sentinel lymph node biopsy was performed in 17% of patients with invasive melanoma, with the main determinant for selection being a Breslow thickness >0.75 mm. The low level of concordance with national guidelines for surgical management of melanoma resulted in overtreatment of many patients. However, a fifth of patients were undertreated, which is likely to have resulted in increased locoregional recurrence rates. The better concordance achieved by physicians treating >30 melanomas per year suggests that a minimum caseload threshold for physicians treating melanoma patients would be desirable. High guideline concordance will ensure patients receive optimal care and minimize morbidity and health service costs.
Publisher: Wiley
Date: 27-03-2013
DOI: 10.1111/PCMR.12069
Publisher: Elsevier BV
Date: 03-2021
Publisher: American Medical Association (AMA)
Date: 08-2016
DOI: 10.1001/JAMADERMATOL.2016.0939
Abstract: Identifying in iduals at high risk of melanoma can optimize primary and secondary prevention strategies. To develop and externally validate a risk prediction model for incident first-primary cutaneous melanoma using self-assessed risk factors. We used unconditional logistic regression to develop a multivariable risk prediction model. Relative risk estimates from the model were combined with Australian melanoma incidence and competing mortality rates to obtain absolute risk estimates. A risk prediction model was developed using the Australian Melanoma Family Study (629 cases and 535 controls) and externally validated using 4 independent population-based studies: the Western Australia Melanoma Study (511 case-control pairs), Leeds Melanoma Case-Control Study (960 cases and 513 controls), Epigene-QSkin Study (44 544, of which 766 with melanoma), and Swedish Women's Lifestyle and Health Cohort Study (49 259 women, of which 273 had melanoma). We validated model performance internally and externally by assessing discrimination using the area under the receiver operating curve (AUC). Additionally, using the Swedish Women's Lifestyle and Health Cohort Study, we assessed model calibration and clinical usefulness. The risk prediction model included hair color, nevus density, first-degree family history of melanoma, previous nonmelanoma skin cancer, and lifetime sunbed use. On internal validation, the AUC was 0.70 (95% CI, 0.67-0.73). On external validation, the AUC was 0.66 (95% CI, 0.63-0.69) in the Western Australia Melanoma Study, 0.67 (95% CI, 0.65-0.70) in the Leeds Melanoma Case-Control Study, 0.64 (95% CI, 0.62-0.66) in the Epigene-QSkin Study, and 0.63 (95% CI, 0.60-0.67) in the Swedish Women's Lifestyle and Health Cohort Study. Model calibration showed close agreement between predicted and observed numbers of incident melanomas across all deciles of predicted risk. In the external validation setting, there was higher net benefit when using the risk prediction model to classify in iduals as high risk compared with classifying all in iduals as high risk. The melanoma risk prediction model performs well and may be useful in prevention interventions reliant on a risk assessment using self-assessed risk factors.
Publisher: Springer Science and Business Media LLC
Date: 11-07-2015
Publisher: Springer Science and Business Media LLC
Date: 18-05-2008
DOI: 10.1038/NG.163
Publisher: Wiley
Date: 30-05-2016
DOI: 10.1002/IJC.30157
Publisher: Cold Spring Harbor Laboratory
Date: 08-12-2017
DOI: 10.1101/231423
Abstract: Most expression quantitative trait loci (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type specific regulatory landscape of human melanocytes, which give rise to melanoma but account for % of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 cis -eQTL SNPs prior to LD-pruning and 4,997 eGenes (FDR .05), which are higher numbers than in any GTEx tissue type with a similar s le size. Melanocyte eQTLs differed considerably from those identified in the 44 GTEx tissues, including skin. Over a third of melanocyte eGenes, including key genes in melanin synthesis pathways, were not observed to be eGenes in two types of GTEx skin tissues or TCGA melanoma s les. The melanocyte dataset also identified cell-type specific trans- eQTLs with a pigmentation-associated SNP for four genes, likely through its cis -regulation of IRF4 , encoding a transcription factor implicated in human pigmentation phenotypes. Melanocyte eQTLs are enriched in cis -regulatory signatures found in melanocytes as well as melanoma-associated variants identified through genome-wide association studies (GWAS). Co-localization of melanoma GWAS variants and eQTLs from melanocyte and skin eQTL datasets identified candidate melanoma susceptibility genes for six known GWAS loci including unique genes identified by the melanocyte dataset. Further, a transcriptome-wide association study using published melanoma GWAS data uncovered four new loci, where imputed expression levels of five genes ( ZFP90, HEBP1, MSC, CBWD1 , and RP11-383H13.1 ) were associated with melanoma at genome-wide significant P -values. Our data highlight the utility of lineage-specific eQTL resources for annotating GWAS findings and present a robust database for genomic research of melanoma risk and melanocyte biology.
Publisher: Springer Science and Business Media LLC
Date: 14-03-2020
Publisher: Oxford University Press (OUP)
Date: 03-02-2020
DOI: 10.1111/BJD.18871
Publisher: BMJ
Date: 2003
DOI: 10.1136/FN.88.1.F15
Abstract: To determine short term morbidity and mortality outcomes, provision of care, and treatments for a national cohort of high risk infants born in 1998-1999 and admitted to New Zealand neonatal intensive care units (NICUs). All level III (six) and level II (13) NICUs in New Zealand. Prospective audit by the Australian and New Zealand Neonatal Network (ANZNN) of all infants defined as "high risk" (born at < 32 weeks gestation or < 1500 g birth weight, or received assisted ventilation for four hours or more, or had major surgery). Data were collected from birth until discharge home or death. There were 3368 high risk infants (3.0% of all live births), comprising 1241 (37%) < 32 weeks gestation, 1084 (32%) < 1500 g, 3156 (94%) who received assisted ventilation, and 243 (7%) who received major surgery (categories overlap). Most infants (87%) received some care in tertiary hospitals, and 13% were cared for entirely in non-tertiary hospitals. Survival was 91% for infants or = 32 weeks gestation who received assisted ventilation, and 92% for infants > or = 32 weeks gestation who had major surgery. The proportion of very preterm infants who survived free of early major morbidity was 11%, 28%, 53%, 81%, and 90% for infants born at < 24, 24-25, 26-27, 28-29, and 30-31 weeks gestation respectively. These unique population based national data provide contemporary information on the care and early morbidity and mortality outcomes for all high risk infants, whether cared for in hospitals with level III or level II NICUs.
Publisher: Springer Science and Business Media LLC
Date: 29-09-2020
DOI: 10.1007/S10689-020-00209-X
Abstract: Germline mutations in CDKN2A greatly increase risk of developing cutaneous melanoma. We have constructed a risk prediction model, Familial Risk Assessment of Melanoma (FRAMe), for estimating the likelihood of carrying a heritable CDKN2A mutation among Australian families, where the prevalence of these mutations is low. Using logistic regression, we analysed characteristics of 299 Australian families recruited through the Sydney site of GenoMEL (international melanoma genetics consortium) with at least three cases of cutaneous melanoma (in situ and invasive) among first-degree blood relatives, for predictors of the presence of a pathogenic CDKN2A mutation. The final multivariable prediction model was externally validated in an independent cohort of 61 melanoma kindreds recruited through GenoMEL Queensland. Family variables independently associated with the presence of a CDKN2A mutation in a multivariable model were number of in iduals diagnosed with melanoma under 40 years of age, number of in iduals diagnosed with more than one primary melanoma, and number of in iduals blood related to a melanoma case in the first degree diagnosed with any cancer excluding melanoma and non-melanoma skin cancer. The number of in iduals diagnosed with pancreatic cancer was not independently associated with mutation status. The risk prediction model had an area under the receiver operating characteristic curve (AUC) of 0.851 (95% CI 0.793, 0.909) in the training dataset, and 0.745 (95%CI 0.612, 0.877) in the validation dataset. This model is the first to be developed and validated using only Australian data, which is important given the higher rate of melanoma in the population. This model will help to effectively identify families suitable for genetic counselling and testing in areas of high ambient ultraviolet radiation. A user-friendly electronic nomogram is available at www.melanomarisk.org.au .
Start Date: 2017
End Date: 2022
Funder: National Health and Medical Research Council
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