Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes.
BJOG
; 127(3): 364-375, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31507061
ABSTRACT
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 (11). 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 OUTCOMEMEASURES:
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 < 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%).CONCLUSION:
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. TWEETABLE ABSTRACT Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
/
Qualidade de Vida
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Genes BRCA1
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Genes BRCA2
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Detecção Precoce de Câncer
/
Síndrome Hereditária de Câncer de Mama e Ovário
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Adult
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Female
/
Humans
/
Male
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article