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

Objective 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. Design Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two‐arms: (i) population‐screening (PS); (ii) FH/clinical‐criteria‐based testing. Setting North London Ashkenazi‐Jewish (AJ) population. Population/Sample AJ women/men. Methods Population‐based RCT (1:1). Participants were recruited through self‐referral, following pre‐test genetic counselling from the North London AJ population. Inclusion criteria: AJ women/men >18 years old; exclusion‐criteria: prior BRCA testing or first‐degree relatives of BRCA‐carriers. Interventions: 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. Main outcome measures 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. Results 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 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