Genital Powder Use and Ovarian Cancer/Reply Cramer, Daniel W; Harlow, Bernard L; Murray, Eleanor J ...
JAMA : the journal of the American Medical Association,
05/2020, Letnik:
323, Številka:
20
Journal Article
Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for ...Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health
. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics
. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.
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 < 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
Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.
Tweetable
Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.
This paper includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights15905
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