ORCID Profile
0000-0003-4081-6883
Current Organisation
University of Aberdeen
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Publisher: Wiley
Date: 13-07-2022
Abstract: Ashkenazi‐Jewish (AJ) population‐based BRCA testing is acceptable, cost‐effective and lifies primary prevention for breast & ovarian cancer. However, data describing lifestyle impact are lacking. We report long‐term results of population‐based BRCA testing on lifestyle behaviour and cancer risk perception. Two‐arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population‐screening (PS) (b) family history (FH)/clinical criteria testing. North London AJ‐population. AJ women/men years. Exclusions: prior BRCA testing or first‐degree relatives of BRCA ‐carriers. Participants were recruited through self‐referral. All participants received informed pre‐test genetic counselling. The intervention included genetic testing for three AJ BRCA ‐mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS arm and participants fulfilling FH/clinical criteria in the FH arm. Patients filled out customised/validated questionnaires at baseline/1‐year/2‐year/3‐year follow‐ups. Generalised linear‐mixed models adjusted for covariates and appropriate contrast tests were used for between‐group/within‐group analysis of lifestyle and behavioural outcomes along with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferroni method), with P 0.0039 considered significant. Lifestyle/behavioural outcomes at baseline/1‐year/2‐year/3‐year follow‐ups. 1034 participants were randomised to PS ( n = 530) or FH ( n = 504) arms. No significant difference was identified between PS‐ and FH‐based BRCA testing approaches in terms of dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/ frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer risk perception decreased with time following BRCA testing, with no difference between FH/PS approaches, and the perception of risk was lowest in BRCA ‐negative participants. Men consumed fewer fruits/vegetables/vitamins and more meat/alcohol than women ( P 0.001). Population‐based and FH‐based AJ BRCA testing have similar long‐term lifestyle impacts on smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer risk perception.
Publisher: Wiley
Date: 10-09-2019
Abstract: Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximise primary prevention for breast-and-ovarian cancer. We compare long-term outcomes of population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life. Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS) (ii) FH/clinical-criteria-based testing. North London Ashkenazi-Jewish (AJ) population. AJ women/men. Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population. AJ women/men >18 years old exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers. Genetic testing for three Jewish BRCA founder-mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality-of-life outcomes over 3 years. Validated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality-of-life outcomes at baseline/1-year/2-year/3-year follow up. In all, 1034 in iduals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety-&-depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health-anxiety (P < 0.0005) and quality-of-life (P = 0.004) scores in both PS and FH groups over time. Eighteen of 30 (60%) BRCA carriers identified did not fulfil clinical criteria for BRCA testing. Total BRCA prevalence was 2.9% (95% CI 1.97-4.12%), BRCA1 prevalence was 1.55% (95% CI 0.89-2.5%) and BRCA2 prevalence was 1.35% (95% CI 0.74-2.26%). Population-based AJ BRCA testing does not adversely affect long-term psychological wellbeing or quality-of-life, decreases anxiety and could identify up to 150% additional BRCA carriers. Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.
Publisher: BMJ
Date: 05-05-2018
DOI: 10.1136/JMEDGENET-2018-105313
Abstract: Genome-wide association studies have identified common SNPs associated with epithelial ovarian cancer (EOC). We evaluated the combined effects of EOC susceptibility SNPs on predicting EOC risk in an independent prospective cohort study. We genotyped ovarian cancer susceptibility single nucleotide polymorphisms (SNPs) in a nested case–control study (750 cases and 1428 controls) from the UK Collaborative Trial of Ovarian Cancer Screening trial. Polygenic risk scores (PRSs) were constructed and their associations with EOC risk were evaluated using logistic regression. The absolute risk of developing ovarian cancer by PRS percentiles was calculated. The association between serous PRS and serous EOC (OR 1.43, 95% CI 1.29 to 1.58, p=1.3×10 –11 ) was stronger than the association between overall PRS and overall EOC risk (OR 1.32, 95% CI 1.21 to 1.45, p=5.4×10 –10 ). Women in the top fifth percentile of the PRS had a 3.4-fold increased EOC risk compared with women in the bottom 5% of the PRS, with the absolute EOC risk by age 80 being 2.9% and 0.9%, respectively, for the two groups of women in the population. PRSs can be used to predict future risk of developing ovarian cancer for women in the general population. Incorporation of PRSs into risk prediction models for EOC could inform clinical decision-making and health management.
Publisher: BMJ Publishing Group Ltd
Date: 11-2019
Publisher: BMJ
Date: 05-04-2018
DOI: 10.1136/JMEDGENET-2017-105195
Abstract: BRCA carrier identification offers opportunities for early diagnoses, targeted treatment and cancer prevention. We evaluate BRCA- carrier detection rates in general and Ashkenazi Jewish (AJ) populations across Greater London and estimate time-to-detection of all identifiable BRCA carriers. BRCA carrier data from 1993 to 2014 were obtained from National Health Service genetic laboratories and compared with modelled predictions of BRCA prevalence from published literature and geographical data from UK Office for National Statistics. Proportion of BRCA carriers identified was estimated. Prediction models were developed to fit BRCA detection rate data. BRCA carrier identification rates were evaluated for an ‘Angelina Jolie effect’. Maps for four Greater London regions were constructed, and their relative BRCA detection rates were compared. Models developed were used to predict future time-to-identify all detectable BRCA carriers in AJ and general populations. Until 2014, only 2.6% (3072/111 742 estimated) general population and 10.9% (548/4985 estimated) AJ population BRCA carriers have been identified in 16 696 608 (AJ=190 997) Greater London population. 57% general population and 54% AJ mutations were identified through cascade testing. Current detection rates mirror linear fit rather than parabolic model and will not identify all BRCA carriers. Addition of unselected ovarian/triple-negative breast cancer testing would take years to identify all BRCA carriers. Doubling current detection rates can identify all ‘detectable’ BRCA carriers in the general population by year 2181, while parabolic and triple linear rates can identify ‘detectable’ BRCA carriers by 2084 and 2093, respectively. The linear fit model can identify ‘detectable’ AJ carriers by 2044. We did not find an Angelina Jolie effect on BRCA carrier detection rates. There was a significant difference in BRCA detection rates between geographical regions over time (P .001). The majority of BRCA carriers have not been identified, missing key opportunities for prevention/earlier diagnosis. Enhanced and new strategies/approaches are needed.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Faiza Gaba.