Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

DR Barnes; MA Rookus; L McGuffog; G Leslie; TM Mooij; J Dennis; N Mavaddat; J Adlard; M Ahmed; K Aittomäki; N Andrieu; IL Andrulis; N Arnold; BK Arun; J Azzollini; J Balmaña; RB Barkardottir; D Barrowdale; J Benitez; P Berthet; K Białkowska; AM Blanco; MJ Blok; B Bonanni; SE Boonen; Å Borg; A Bozsik; AR Bradbury; P Brennan; C Brewer; J Brunet; SS Buys; T Caldés; MA Caligo; I Campbell; LL Christensen; WK Chung; KBM Claes; C Colas; MA Collonge-Rame; C Delnatte; L Faivre; S Giraud; C Lasset; V Mari; N Mebirouk; E Mouret-Fourme; H Schuster; D Stoppa-Lyonnet; A Antoniou; J Cook; R Davidson; D Easton; R Eeles; DG Evans; D Frost; H Hanson; L Izatt; KR Ong; L Side; A O’Shaughnessy-Kirwan; M Tischkowitz; L Walker; MB Daly; M de la Hoya; R de Putter; P Devilee; O Diez; YC Ding; SM Domchek; CM Dorfling; M Dumont; B Ejlertsen; C Engel; L Foretova; F Fostira; M Friedlander; E Friedman; PA Ganz; J Garber; A Gehrig; AM Gerdes; P Gesta; G Glendon; AK Godwin; DE Goldgar

Journal article

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

DR Barnes, MA Rookus, L McGuffog, G Leslie, TM Mooij, J Dennis, N Mavaddat, J Adlard, M Ahmed, K Aittomäki, N Andrieu, IL Andrulis, N Arnold, BK Arun, J Azzollini, J Balmaña, RB Barkardottir, D Barrowdale, J Benitez, P Berthet Show all

Genetics in Medicine | ELSEVIER SCIENCE INC | Published : 2020

DOI: 10.1038/s41436-020-0862-x

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Abstract

Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. Methods: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)–negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results: The ER-negative PRS showed the strongest association with BC risk..

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