Can population BRCA screening be applied in non-Ashkenazi Jewish populations? Experience in Macau population

Published on Sep 1, 2021in Journal of Medical Genetics4.943
· DOI :10.1136/JMEDGENET-2020-107181
Hui Dong (SJTU: Shanghai Jiao Tong University)
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Abstract
Background Pathogenic mutation in BRCA genes causes high cancer risk. Identifying the mutation carriers plays key roles in preventing BRCA mutation-related cancer. Population screening has demonstrated its power for comprehensive identification of the mutation carriers. However, it is only recommended for the Ashkenazi Jewish population with high prevalence of three founder mutations, but not for non-Ashkenazi Jewish populations as the cost-effectiveness could be too low due to their lower mutation prevalence and lack of founder mutation. Population screening would not benefit the majority of the human population for BRCA mutation-related cancer prevention. Methods We used population BRCA screening in 6000 residents, 1% of the Macau population, an ethnic Chinese population with unique genetic, linguistic and cultural features, and its BRCA mutation has not been analysed before. Results We called BRCA variants, identified 18 carriers with 14 pathogenic mutations and determined the prevalence of 0.29% in the population (95% CI 0.15% to 0.42%). We compared the testing cost between the Ashkenazi Jewish population, the Sephardi Jewish population and the Macau population, and observed only a few fold differences. Conclusion Our study shows that testing cost is not the most important factor in considering population BRCA screening, at least for the populations in the developed countries/regions, regardless of the status of mutation prevalence and founder mutation.
References21
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Importance Detection of disease-associated variants in theBRCA1andBRCA2(BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals. Objectives To identify pathogenic and likely pathogenic (P/LP)BRCA1/2variants in an unselected research cohort, and to characterize the features associated with P/LP variants. Design, Setting, and Participants This is a cross-sectional study of adult volunteers (n = 50 726) who underwent exome sequencing at a single health care system (...
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J.S. Brown, B. O'Carrigan, and T.A. Yap acknowledge support from the Experimental Cancer Medicine Centre (to The Institute of Cancer Research) and the National Institute for Health Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research). Research in The Jackson laboratory is funded by Cancer Research UK (CRUK) program grant number C6/A18796. Core funding is provided by CRUK (C6946/A14492) and the Wellcome Trust (WT092096). S.P....
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