Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes.

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 >18years 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 3years. 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 individuals (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 3years. 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.