ORCID Profile
0000-0003-3714-8386
Current Organisations
Deakin University
,
Cancer Council Victoria
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Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516093
Abstract: Supplementary Figure 3 shows scatter plots with the genetic association with folate on the x-axis andthe genetic association with ovarian cancer on the y-axis, for (A) women with and (B) without endometriosis. The regression line for the inverse variance weighted Mendelian randomization method is shown.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.C.6695948.V1
Abstract: AbstractBackground: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer however, whether high folate intake increases risk in this group is unknown. Methods: We conducted a pooled analysis of six case–control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. Results: Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01–1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. Conclusions: High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. Impact: Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group. /
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.C.6695948.V2
Abstract: AbstractBackground: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer however, whether high folate intake increases risk in this group is unknown. Methods: We conducted a pooled analysis of six case–control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. Results: Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01–1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. Conclusions: High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. Impact: Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group. /
Publisher: Springer Science and Business Media LLC
Date: 28-03-2017
DOI: 10.1038/BJC.2017.68
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516090
Abstract: Supplementary Table 1 shows the range of folate intake included in each tertile, by OCAC study site.
Publisher: Cambridge University Press (CUP)
Date: 21-01-2021
DOI: 10.1017/S1368980021000197
Abstract: To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD). Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and in idual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined. Melbourne, Australia. A cohort of 20 926 participants (62 % women) aged 40–59 years at recruitment between 1990 and 1994. For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d 95 % CI 1·01, 1·09 P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d 95 % CI 0·82, 0·98 P = 0·010) and starch intakes (OR 0·84 per 30 g/d 95 % CI 0·75, 0·94 P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores. Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814258.V1
Abstract: Supplementary Table 5 shows the results from the different Mendelian randomization methods investigating the association between genetically predicted folate and risk of ovarian cancer, by endometriosis status
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814273.V1
Abstract: Supplementary Table 2 shows the single nucleotide polymorphisms (SNPs) used as instruments for folate level in the Mendelian randomization analysis.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2015
DOI: 10.1158/1538-7445.AM2015-881
Abstract: INTRODUCTION: Observational studies have reported positive associations between higher body mass index (BMI) and risks of borderline ovarian tumors and non-high grade serous ovarian cancer (non-HGSC), but the lack of association observed for HGSC may be due to bias arising from weight loss before diagnosis. Observational studies also suggest a positive association between greater height and ovarian cancer risk, but confounding factors may be obscuring the true relationship. The Mendelian randomization (MR) technique uses genetic markers as proxies for environmental risk factors, and can overcome the limitations of bias and confounding which affect observational studies. AIM / METHODS: This study used MR to elucidate the relationship between body size (BMI and height) and risk of ovarian cancer. We pooled data from 16,395 cases and 23,003 controls, all genetically European, from 39 studies in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS) for each trait, summing trait-increasing alleles at 31 single nucleotide polymorphisms (SNPs) associated with BMI and 609 SNPs associated with height in genome-wide association studies, weighting alleles by published β-coefficients for their effect on the trait. Each GRS was a strong instrument for the trait (F-statistics 33.8 [BMI] and 516 [height]). In a two-stage predictor substitution MR approach, we used multivariate logistic regression to model case-control status on body size predicted by each GRS. Study-specific estimates per 5-unit increase in predicted BMI or height were pooled to generate pooled odds ratios (OR) and 95% confidence intervals (CI) using random-effects meta-analysis. Our primary hypotheses were that genetic BMI would be associated with increased risk of non-HGSC but not HGSC and genetic height would be associated with increased risk of ovarian cancer overall. RESULTS: Higher genetically-predicted BMI was associated with increased risk of non-HGSC cancer (OR 1.37, 95% CI 1.02-1.83 per 5-unit increase) but not HGSC (OR 1.05, 95% CI 0.83-1.33). In secondary analyses stratified by behavior/subtype, the strongest association was seen for low grade/borderline serous cancers (OR 2.02, 95% CI 1.24-3.30). Women with greater genetically-predicted height had a modestly increased risk of all (invasive and borderline) ovarian tumors (OR 1.06, 95% CI 1.01-1.11 per 5 cm). In secondary analyses stratified by histologic subtype, the strongest association was seen for clear cell cancers (OR 1.20, 95% CI 1.04-1.38). CONCLUSION: This study is the first to apply MR to investigate ovarian cancer risk factors. These data confirm results from epidemiologic studies, suggesting that obesity is causally associated with non-HGSC, but does not increase risk of the most common HGSC subtype. They also support an association between height and ovarian cancer. Citation Format: Suzanne C. Dixon, Christina M. Nagle, Aaron P. Thrift, Paul D.P Pharoah, Ailith Pirie, Celeste Leigh Pearce, Wei Zheng, Penelope M. Webb, for the Ovarian Cancer Association Consortium. Association of adult body mass index and height with risk of ovarian cancer in 39,000 women: Results of a Mendelian randomization study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research 2015 Apr 18-22 Philadelphia, PA. Philadelphia (PA): AACR Cancer Res 2015 (15 Suppl):Abstract nr 881. doi:10.1158/1538-7445.AM2015-881
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516084.V1
Abstract: Supplementary Table 3 shows the associations between folate intake (dietary, supplemental, total) and ovarian cancer by endometriosis status, and by histological subtype (endometrioid/clear cell cancers and high grade serous cancers).
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814258
Abstract: Supplementary Table 5 shows the results from the different Mendelian randomization methods investigating the association between genetically predicted folate and risk of ovarian cancer, by endometriosis status
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814267.V1
Abstract: Supplementary Table 3 shows the associations between folate intake (dietary, supplemental, total) and ovarian cancer by endometriosis status, and by histological subtype (endometrioid/clear cell cancers and high grade serous cancers).
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516093.V1
Abstract: Supplementary Figure 3 shows scatter plots with the genetic association with folate on the x-axis andthe genetic association with ovarian cancer on the y-axis, for (A) women with and (B) without endometriosis. The regression line for the inverse variance weighted Mendelian randomization method is shown.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516099
Abstract: Supplementary Figure 1 shows a flowchart of exclusions to obtain the study population, with the number of cases and controls eligible for the analysis.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516078.V1
Abstract: Supplementary Table 5 shows the results from the different Mendelian randomization methods investigating the association between genetically predicted folate and risk of ovarian cancer, by endometriosis status
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516096
Abstract: Supplementary Figure 2 shows two forest plots depicting the association between (A) dietary folate intake and (B) supplemental folate intake and ovarian cancer for women with endometriosis, stratified by potential effect modifiers
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814252
Abstract: Characteristics of cases and controls with and without endometriosis.
Publisher: Elsevier BV
Date: 11-2020
Publisher: American Association for Cancer Research (AACR)
Date: 02-06-2022
DOI: 10.1158/1055-9965.EPI-22-0234
Abstract: Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. In a case–control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007–2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990–1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03–2.75] and 2.28-fold (95% CI, 1.27–4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56% P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814276.V1
Abstract: Supplementary Table 1 shows the range of folate intake included in each tertile, by OCAC study site.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814249.V1
Abstract: Median folate intake and mandatory folate fortification status, OCAC studies.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814282.V1
Abstract: Supplementary Figure 2 shows two forest plots depicting the association between (A) dietary folate intake and (B) supplemental folate intake and ovarian cancer for women with endometriosis, stratified by potential effect modifiers
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516081.V1
Abstract: Supplementary Table 4 shows the association between glycemic index, glycemic load, grain intake and risk of ovarian cancer for women with and without endometriosis.
Publisher: Oxford University Press (OUP)
Date: 13-06-2019
DOI: 10.1093/JNCI/DJZ121
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516096.V1
Abstract: Supplementary Figure 2 shows two forest plots depicting the association between (A) dietary folate intake and (B) supplemental folate intake and ovarian cancer for women with endometriosis, stratified by potential effect modifiers
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814249
Abstract: Median folate intake and mandatory folate fortification status, OCAC studies.
Publisher: BMJ
Date: 06-09-2022
DOI: 10.1136/BJSPORTS-2021-105132
Abstract: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre ost-menopause, and by case-groups defined by tumour characteristics. We performed two-s le inverse-variance-weighted MR using in idual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105–377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (n snps =5) or sedentary time (n snps =6), or accelerometer-measured (n snps =1) or self-reported (n snps =5) vigorous physical activity. Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD ~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre erimenopausal breast cancer (OR=0.62 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
Publisher: University of Queensland Library
Date: 2020
DOI: 10.14264/B83D31A
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814243
Abstract: Association between folate intake and risk of invasive epithelial ovarian cancer, by endometriosis status.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.C.6695948
Abstract: AbstractBackground: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer however, whether high folate intake increases risk in this group is unknown. Methods: We conducted a pooled analysis of six case–control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. Results: Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01–1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. Conclusions: High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. Impact: Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group. /
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814282
Abstract: Supplementary Figure 2 shows two forest plots depicting the association between (A) dietary folate intake and (B) supplemental folate intake and ovarian cancer for women with endometriosis, stratified by potential effect modifiers
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814285
Abstract: Supplementary Figure 1 shows a flowchart of exclusions to obtain the study population, with the number of cases and controls eligible for the analysis.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814279.V1
Abstract: Supplementary Figure 3 shows scatter plots with the genetic association with folate on the x-axis and the genetic association with ovarian cancer on the y-axis, for (A) women with and (B) without endometriosis. The regression line for the inverse variance weighted Mendelian randomization method is shown.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814252.V1
Abstract: Characteristics of cases and controls with and without endometriosis.
Publisher: Springer Science and Business Media LLC
Date: 16-06-2021
Publisher: BMJ
Date: 09-2017
DOI: 10.1097/IGC.0000000000001039
Abstract: The role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity. From a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ 2 tests. Median follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a “high-risk” group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P 0.0001). In this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814285.V1
Abstract: Supplementary Figure 1 shows a flowchart of exclusions to obtain the study population, with the number of cases and controls eligible for the analysis.
Publisher: Informa UK Limited
Date: 05-06-2014
DOI: 10.3109/13625187.2014.919380
Abstract: A comprehensive life course perspective of women's experiences in obtaining and using contraception in Australia is lacking. This paper explores free-text comments about contraception provided by women born between 1973 and 1978 who participated in the Australian Longitudinal Study on Women's Health (ALSWH). The ALSWH is a national population-based cohort study involving over 40,000 women from three age groups, who are surveyed every three years. An initial search identified 1600 comments from 690 women across five surveys from 1996 (when they were aged 18-23 years) to 2009 (31-36 years). The analysis included 305 comments from 289 participants. Factors relating to experiences of barriers to access and optimal contraceptive use were identified and explored using thematic analysis. Five themes recurred across the five surveys as women aged: (i) side effects affecting physical and mental health (ii) lack of information about contraception (iii) negative experiences with health services (iv) contraceptive failure and (v) difficulty with accessing contraception. Side effects of hormonal contraception and concerns about contraceptive failure influence women's mental and physical health. Many barriers to effective contraception persist throughout women's reproductive lives. Further research is needed into reducing barriers and minimising negative experiences, to ensure optimal contraceptive access for Australian women.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2021
DOI: 10.1038/S41467-020-20368-W
Abstract: Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516099.V1
Abstract: Supplementary Figure 1 shows a flowchart of exclusions to obtain the study population, with the number of cases and controls eligible for the analysis.
Publisher: Oxford University Press (OUP)
Date: 11-02-2019
DOI: 10.1093/JNCI/DJZ015
Abstract: Recent studies have called into question the long-held belief that hysterectomy without oophorectomy protects against ovarian cancer. This population-based longitudinal record-linkage study aimed to explore this relationship, overall and by age at hysterectomy, time period, surgery type, and indication for hysterectomy. We followed the female adult Western Australian population (837 942 women) across a 27-year period using linked electoral, hospital, births, deaths, and cancer records. Surgery dates were determined from hospital records, and ovarian cancer diagnoses (n = 1640) were ascertained from cancer registry records. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer incidence. Hysterectomy without oophorectomy (n = 78 594) was not associated with risk of invasive ovarian cancer overall (HR = 0.98, 95% CI = 0.85 to 1.11) or with the most common serous subtype (HR = 1.05, 95% CI = 0.89 to 1.23). Estimates did not vary statistically significantly by age at procedure, time period, or surgical approach. However, among women with endometriosis (5.8%) or with fibroids (5.7%), hysterectomy was associated with substantially decreased ovarian cancer risk overall (HR = 0.17, 95% CI = 0.12 to 0.24, and HR = 0.27, 95% CI = 0.20 to 0.36, respectively) and across all subtypes. Our results suggest that for most women, having a hysterectomy with ovarian conservation is not likely to substantially alter their risk of developing ovarian cancer. However, our results, if confirmed, suggest that ovarian cancer risk reduction could be considered as a possible benefit of hysterectomy when making decisions about surgical management of endometriosis or fibroids.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814279
Abstract: Supplementary Figure 3 shows scatter plots with the genetic association with folate on the x-axis and the genetic association with ovarian cancer on the y-axis, for (A) women with and (B) without endometriosis. The regression line for the inverse variance weighted Mendelian randomization method is shown.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.YGYNO.2013.12.025
Abstract: Folate is essential for DNA synthesis and methylation and is implicated in tumour progression. Few studies have examined its role in ovarian cancer survival. Our objective was to determine relationships between intake of folate, related one-carbon nutrients, single nucleotide polymorphisms (SNPs) in folate-metabolising genes and survival following ovarian cancer diagnosis. This analysis included 1270 women with invasive epithelial ovarian cancer diagnosed in 2002-2006. Pre-diagnostic and some post-diagnostic lifestyle, dietary, and sociodemographic information was collected via self-administered questionnaires. DNA s les were genotyped for SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) genes. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Multivariate analyses did not identify associations between higher pre-diagnostic intake of folate, folic acid, vitamins B2, B6, and B12, methionine, betaine or choline and survival overall. In stratified analyses, higher folic acid and folate intake was associated with significantly worse survival among women with mucinous tumours (HRs per 100 μg 1.30 and 1.43, respectively) and smokers (HRs per 100 μg 1.23 and 1.16 respectively). There was also a suggestion that higher supplemental folic acid use post-diagnosis was associated with worse survival (HR per 100 μg 1.03, 95%CI 1.00-1.05). MTHFR SNP rs2066470 was significantly associated with survival (per allele HR 0.81, 95%CI 0.67-0.98). Our data provide little evidence that folate intake affects ovarian cancer survival. However, combined effects with smoking, and findings within the mucinous subtype and for post-diagnosis folic acid, warrant further investigation.
Publisher: Elsevier BV
Date: 06-2021
Publisher: American Association for Cancer Research (AACR)
Date: 20-10-2022
DOI: 10.1158/1055-9965.EPI-21-0438
Abstract: We undertook a systematic review and appraised the evidence for an effect of circulating sex steroid hormones and sex hormone–binding globulin (SHBG) on breast cancer risk in pre- and postmenopausal women. Systematic searches identified prospective studies relevant to this review. Meta-analyses estimated breast cancer risk for women with the highest compared with the lowest level of sex hormones, and the DRMETA Stata package was used to graphically represent the shape of these associations. The ROBINS-E tool assessed risk of bias, and the GRADE system appraised the strength of evidence. In premenopausal women, there was little evidence that estrogens, progesterone, or SHBG were associated with breast cancer risk, whereas androgens showed a positive association. In postmenopausal women, higher estrogens and androgens were associated with an increase in breast cancer risk, whereas higher SHBG was inversely associated with risk. The strength of the evidence quality ranged from low to high for each hormone. Dose–response relationships between sex steroid hormone concentrations and breast cancer risk were most notable for postmenopausal women. These data support the plausibility of a role for sex steroid hormones in mediating the causal relationship between physical activity and the risk of breast cancer. See related reviews by Lynch et al., p. 11 and Swain et al., p. 16
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814276
Abstract: Supplementary Table 1 shows the range of folate intake included in each tertile, by OCAC study site.
Publisher: Oxford University Press (OUP)
Date: 04-09-2021
DOI: 10.1093/IJE/DYAB181
Abstract: Questions remain about the effect on mortality of physical activity and sedentary behaviour over time. We summarized the evidence from studies that assessed exposure from multiple time points and critiqued the analytic approaches used. A search was performed on MEDLINE, Embase, Emcare, Scopus and Web of Science up to January 2021 for studies of repeatedly assessed physical activity or sedentary behaviour in relation to all-cause or cause-specific mortality. Relative risks from in idual studies were extracted. Each study was assessed for risk of bias from multiple domains. We identified 64 eligible studies (57 on physical activity, 6 on sedentary behaviour, 1 on both). Cox regression with a time-fixed exposure history (n = 45) or time-varying covariates (n = 13) were the most frequently used methods. Only four studies used g-methods, which are designed to adjust for time-varying confounding. Risk of bias arose primarily from inadequate adjustment for time-varying confounders, participant selection, exposure classification and changes from measured exposure. Despite heterogeneity in methods, most studies found that being consistently or increasingly active over adulthood was associated with lower all-cause and cardiovascular-disease mortality compared with being always inactive. Few studies examined physical-activity changes and cancer mortality or effects of sedentary-behaviour changes on mortality outcomes. Accumulating more evidence using longitudinal data while addressing the methodological challenges would provide greater insight into the health effects of initiating or maintaining a more active and less sedentary lifestyle.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516078
Abstract: Supplementary Table 5 shows the results from the different Mendelian randomization methods investigating the association between genetically predicted folate and risk of ovarian cancer, by endometriosis status
Publisher: American Association for Cancer Research (AACR)
Date: 20-10-2021
DOI: 10.1158/1055-9965.EPI-21-0437
Abstract: The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorticoids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity–sex hormone–breast cancer pathway. The confirmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer. See related reviews by Lynch et al., p. 11 and Drummond et al., p. 28
Publisher: Human Kinetics
Date: 2020
Abstract: Background : It is not always clear whether physical activity is causally related to health outcomes, or whether the associations are induced through confounding or other biases. Randomized controlled trials of physical activity are not feasible when outcomes of interest are rare or develop over many years. Thus, we need methods to improve causal inference in observational physical activity studies. Methods : We outline a range of approaches that can improve causal inference in observational physical activity research, and also discuss the impact of measurement error on results and methods to minimize this. Results : Key concepts and methods described include directed acyclic graphs, quantitative bias analysis, Mendelian randomization, and potential outcomes approaches which include propensity scores, g methods, and causal mediation. Conclusions : We provide a brief overview of some contemporary epidemiological methods that are beginning to be used in physical activity research. Adoption of these methods will help build a stronger body of evidence for the health benefits of physical activity.
Publisher: American Association for Cancer Research (AACR)
Date: 22-02-2021
DOI: 10.1158/1055-9965.EPI-20-1670
Abstract: This study aimed to investigate the associations between hysterectomy for benign indications and risk of breast, colorectal, kidney, and thyroid cancer, and to explore whether these associations are modified by removal of ovaries at the time of surgery or by age at surgery. We conducted a retrospective cohort study of the female population of Western Australia (n = 839,332) linking data from electoral, hospital, births, deaths, and cancer records. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the associations between hysterectomy and diagnosis of breast, colorectal, kidney, and thyroid cancers. Compared with no surgery, hysterectomy without oophorectomy (hysterectomy) and hysterectomy with bilateral salpingo-oophorectomy (hysterectomy-BSO) were associated with higher risk of kidney cancer (HR, 1.32 95% CI, 1.11–1.56 and HR, 1.29 95% CI, 0.96–1.73, respectively). Hysterectomy, but not hysterectomy-BSO, was related to higher risk of thyroid cancer (HR, 1.38 95% CI, 1.19–1.60). In contrast, hysterectomy (HR, 0.94 95% CI, 0.90–0.98) and hysterectomy-BSO (HR, 0.92 95% CI, 0.85–1.00) were associated with lower risk of breast cancer. We found no association between hysterectomy status and colorectal cancer. The associations between hysterectomy and cancer varied by cancer type with increased risks for thyroid and kidney cancer, decreased risk for breast cancer, and no association for colorectal cancer. As breast, colorectal, and gynecologic cancers comprise a sizeable proportion of all cancers in women, our results suggest that hysterectomy is unlikely to increase overall cancer risk however, further research to understand the higher risk of thyroid and kidney cancer is warranted.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814273
Abstract: Supplementary Table 2 shows the single nucleotide polymorphisms (SNPs) used as instruments for folate level in the Mendelian randomization analysis.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516081
Abstract: Supplementary Table 4 shows the association between glycemic index, glycemic load, grain intake and risk of ovarian cancer for women with and without endometriosis.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516087.V1
Abstract: Supplementary Table 2 shows the single nucleotide polymorphisms (SNPs) used as instruments for folate level in the Mendelian randomization analysis.
Publisher: American Association for Cancer Research (AACR)
Date: 23-05-2023
DOI: 10.1158/1055-9965.EPI-23-0121
Abstract: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer however, whether high folate intake increases risk in this group is unknown. We conducted a pooled analysis of six case–control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01–1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Springer Science and Business Media LLC
Date: 20-03-2018
Publisher: American Association for Cancer Research (AACR)
Date: 08-2015
DOI: 10.1158/1538-7445.AM2015-4637
Abstract: Introduction Previous observational studies investigating height, body mass index and serum lipid levels as prognostic factors in ovarian cancer have been inconclusive. In addition to possible influences of reverse causation, it is possible that factors such as diet, socio-economic status and other lifestyle factors are confounding true associations. Mendelian Randomization (MR) utilises genotype data for variants associated with phenotypes of interest to create genetic risk scores for these modifiable exposures. One advantage of using genetic markers as proxies is that they are determined from birth and are therefore unaffected by confounding variables. We aim to use MR to investigate the association between height, BMI and serum lipid levels (high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides) and ovarian cancer prognosis in the absence of confounding variables. Methods We used data from 12,908 invasive ovarian cancer cases with 5,813 events from 26 studies in the Ovarian Cancer Association Consortium. All in iduals were of European ancestry. We calculated genetic risk scores for each in idual for height, BMI and serum lipids by taking the sum of the alleles associated with the trait, weighted by the size of their effect on the trait. The genetic risk scores were then included in a Cox proportional hazards model adjusted for study and two principal components to test for association with prognosis. For the analysis of height, we included 422 uncorrelated single nucleotide polymorphisms identified by the Genetic Investigation of Anthropometric Traits (GIANT) consortium as associated with height at genome-wide significance. In the analysis of BMI, we included 32 SNPs associated with BMI in analyses by the GIANT consortium. In order to account for the pleiotropy between the three lipid types we included the genetic risk scores for each of the three traits in a joint analysis. SNPs identified by the Global Lipids Genetics Consortium as associated with lipid levels were included: 95 with HDL, 82 with LDL and 64 with triglycerides. Results We found no evidence of association between the five genetic risk scores and ovarian cancer prognosis. The genetic risk score for height had an estimated hazard ratio of 1.01, 95% confidence interval 0.94 - 1.08, p-value = 0.82. The hazard ratio for BMI was 1.00, 95% CI 0.95 - 1.05, p-value = 0.99. The hazard ratios for HDL, LDL and triglycerides were 1.03(0.94-1.13), 1.02(0.94-1.12) and 1.08(0.96-1.21) respectively with p-values = 0.53, 0.58 and 0.19. Conclusion Our study does not provide any evidence of association between height, BMI and serum lipid levels and ovarian cancer prognosis. Citation Format: Ailith Pirie, Suzanne C. Dixon, Penelope M. Webb, Wei Zheng, Paul D. P. Pharoah, on behalf of the Ovarian Cancer Association Consortium. The effect of height, BMI and serum lipid levels on ovarian cancer prognosis in over 12,000 women: a Mendelian randomization study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research 2015 Apr 18-22 Philadelphia, PA. Philadelphia (PA): AACR Cancer Res 2015 (15 Suppl):Abstract nr 4637. doi:10.1158/1538-7445.AM2015-4637
Publisher: Springer Science and Business Media LLC
Date: 07-07-2015
DOI: 10.1038/BJC.2015.245
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814243.V1
Abstract: Association between folate intake and risk of invasive epithelial ovarian cancer, by endometriosis status.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814264.V1
Abstract: Supplementary Table 4 shows the association between glycemic index, glycemic load, grain intake and risk of ovarian cancer for women with and without endometriosis.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814264
Abstract: Supplementary Table 4 shows the association between glycemic index, glycemic load, grain intake and risk of ovarian cancer for women with and without endometriosis.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/1055-9965.23814267
Abstract: Supplementary Table 3 shows the associations between folate intake (dietary, supplemental, total) and ovarian cancer by endometriosis status, and by histological subtype (endometrioid/clear cell cancers and high grade serous cancers).
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516087
Abstract: Supplementary Table 2 shows the single nucleotide polymorphisms (SNPs) used as instruments for folate level in the Mendelian randomization analysis.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516090.V1
Abstract: Supplementary Table 1 shows the range of folate intake included in each tertile, by OCAC study site.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2023
DOI: 10.1158/1055-9965.23516084
Abstract: Supplementary Table 3 shows the associations between folate intake (dietary, supplemental, total) and ovarian cancer by endometriosis status, and by histological subtype (endometrioid/clear cell cancers and high grade serous cancers).
No related grants have been discovered for Suzanne Dixon-Suen.