{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T21:47:21Z","timestamp":1788040041088,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T00:00:00Z","timestamp":1568073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"\u2018The Eve Appeal\u2019 charity"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2020,2]]},"abstract":"Objective<\/jats:title>Unselected population\u2010based BRCA<\/jats:styled-content><\/jats:italic> testing provides the opportunity to apply genomics on a population\u2010scale to maximise primary prevention for breast\u2010and\u2010ovarian cancer. We compare long\u2010term outcomes of population\u2010based and family\u2010history (FH<\/jats:styled-content>)\/clinical\u2010criteria\u2010based BRCA<\/jats:styled-content><\/jats:italic> testing on psychological health and quality of life.<\/jats:p><\/jats:sec>Design<\/jats:title>Randomised controlled trial (RCT<\/jats:styled-content>) (ISRCTN<\/jats:styled-content>73338115) GC<\/jats:styled-content>aPPS<\/jats:styled-content>, with two\u2010arms: (i) population\u2010screening (PS<\/jats:styled-content>); (ii) FH<\/jats:styled-content>\/clinical\u2010criteria\u2010based testing.<\/jats:p><\/jats:sec>Setting<\/jats:title>North London Ashkenazi\u2010Jewish (AJ<\/jats:styled-content>) population.<\/jats:p><\/jats:sec>Population\/Sample<\/jats:title>AJ<\/jats:styled-content> women\/men.<\/jats:p><\/jats:sec>Methods<\/jats:title>Population\u2010based RCT<\/jats:styled-content> (1:1). Participants were recruited through self\u2010referral, following pre\u2010test genetic counselling from the North London AJ<\/jats:styled-content> population.<\/jats:p>Inclusion criteria<\/jats:italic>: AJ<\/jats:styled-content> women\/men >18\u00a0years old; exclusion\u2010criteria: prior BRCA<\/jats:styled-content><\/jats:italic> testing or first\u2010degree relatives of BRCA<\/jats:styled-content><\/jats:italic>\u2010carriers.<\/jats:p>Interventions<\/jats:italic>: Genetic testing for three Jewish BRCA<\/jats:styled-content><\/jats:italic> founder\u2010mutations: 185delAG<\/jats:styled-content> (c.68_69delAG<\/jats:styled-content>), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS<\/jats:styled-content> arm; (ii) those fulfilling FH<\/jats:styled-content>\/clinical criteria in FH<\/jats:styled-content> arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA<\/jats:styled-content><\/jats:italic> testing on psychological and quality\u2010of\u2010life outcomes over 3\u00a0years.<\/jats:p><\/jats:sec>Main outcome measures<\/jats:title>Validated questionnaires (HADS<\/jats:styled-content>\/MICRA<\/jats:styled-content>\/HAI<\/jats:styled-content>\/SF<\/jats:styled-content>12) used to analyse psychological wellbeing\/quality\u2010of\u2010life outcomes at baseline\/1\u2010year\/2\u2010year\/3\u2010year follow up.<\/jats:p><\/jats:sec>Results<\/jats:title>In all, 1034 individuals (691 women, 343 men) were randomised to PS<\/jats:styled-content> (n<\/jats:italic>\u00a0=\u00a0530) or FH<\/jats:styled-content> (n<\/jats:italic>\u00a0=\u00a0504) arms. There was a statistically significant decrease in anxiety (P<\/jats:italic>\u00a0=\u00a00.046) and total anxiety\u2010&\u2010depression scores (P<\/jats:italic>\u00a0=\u00a00.0.012) in the PS<\/jats:styled-content> arm compared with the FH<\/jats:styled-content> arm over 3\u00a0years. No significant difference was observed between the FH<\/jats:styled-content> and PS<\/jats:styled-content> arms for depression, health\u2010anxiety, distress, uncertainty, quality\u2010of\u2010life or experience scores associated with BRCA<\/jats:styled-content><\/jats:italic> testing. Contrast tests showed a decrease in anxiety (P<\/jats:italic>\u00a0=\u00a00.018), health\u2010anxiety (P<\/jats:italic>\u00a0<\u00a00.0005) and quality\u2010of\u2010life (P<\/jats:italic>\u00a0=\u00a00.004) scores in both PS<\/jats:styled-content> and FH<\/jats:styled-content> groups over time. Eighteen of 30 (60%) BRCA<\/jats:styled-content><\/jats:italic> carriers identified did not fulfil clinical criteria for BRCA<\/jats:styled-content><\/jats:italic> testing. Total BRCA<\/jats:styled-content><\/jats:italic> prevalence was 2.9% (95% CI<\/jats:styled-content> 1.97\u20134.12%), BRCA<\/jats:styled-content>1<\/jats:italic> prevalence was 1.55% (95% CI<\/jats:styled-content> 0.89\u20132.5%) and BRCA<\/jats:styled-content>2<\/jats:italic> prevalence was 1.35% (95% CI<\/jats:styled-content> 0.74\u20132.26%).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Population\u2010based AJ <\/jats:styled-content>BRCA<\/jats:styled-content><\/jats:italic> testing does not adversely affect long\u2010term psychological wellbeing or quality\u2010of\u2010life, decreases anxiety and could identify up to 150% additional BRCA<\/jats:styled-content><\/jats:italic> carriers.<\/jats:p><\/jats:sec>Tweetable abstract<\/jats:title>Population BRCA<\/jats:styled-content><\/jats:italic> testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of 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