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

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Barnes, DR (Author) Other; Rookus, MA (Author) Other; McGuffog, L (Author) Other; Leslie, G (Author) Other; Mooij, TM (Author) Other; Dennis, J (Author) Other; Mavaddat, N (Author) Other; Adlard, J (Author) Other; Ahmed, M (Author) Other; Aittomaki, K (Author) Other; Andrieu, N (Author) Other; Andrulis, IL (Author) Other; Arnold, N (Author) Other; Arun, BK (Author) Other; Azzollini, J (Author) Other; Balmana, J (Author) Other; Barkardottir, RB (Author) Other; Barrowdale, D (Author) Other; Benitez, J (Author) Other; Berthet, P (Author) Other; Bialkowska, K (Author) Other; Blanco, AM (Author) Other; Blok, MJ (Author) Other; Bonanni, B (Author) Other; Boonen, SE (Author) Other; Borg, A (Author) Other; Bozsik, A (Author) Other; Bradbury, AR (Author) Other; Brennan, P (Author) Other; Brewer, C (Author) Other; Brunet, J (Author) Other; Buys, SS (Author) Other; Caldes, T (Author) Other; Caligo, MA (Author) Other; Campbell, I (Author) Other; Christensen, LL (Author) Other; Chung, WK (Author) Other; Claes, KBM (Author) Other; Colas, C (Author) Other; Collonge Rame, MA (Author) Other; Cook, J (Author) Other; Daly, MB (Author) Other; Davidson, R (Author) Other; de la Hoya, M (Author) Other; de Putter, R (Author) Other; Delnatte, C (Author) Other; Devilee, P (Author) Other; Diez, O (Author) Other; Ding, YC (Author) Other; Domchek, SM (Author) Other; Dorfling, CM (Author) Other; Dumont, M (Author) Other; Eeles, R (Author) Other; Ejlertsen, B (Author) Other; Engel, C (Author) Other; Evans, DG (Author) Other; Faivre, L (Author) Other; Foretova, L (Author) Other; Fostira, F (Author) Other; Friedlander, M (Author) Other; Friedman, E (Author) Other; Frost, D (Author) Other; Ganz, PA (Author) Other; Garber, J (Author) Other; Gehrig, A (Author) Other; Gerdes, AM (Author) Other; Gesta, P (Author) Other; Giraud, S (Author) Other; Glendon, G (Author) Other; Godwin, AK (Author) Other; Goldgar, DE (Author) Other; Gonzalez Neira, A (Author) Other; Greene, MH (Author) Other; Gschwantler Kaulich, D (Author) Other; Hahnen, E (Author) Other; Hamann, U (Author) Other; Hanson, H (Author) Other; Hentschel, J (Author) Other; Hogervorst, FBL (Author) Other; Hooning, MJ (Author) Other; Horvath, J (Author) Other; Hu, CL (Author) Other; Hulick, PJ (Author) Other; Imyanitov, EN (Author) Other; Isaacs, C (Author) Other; Izatt, L (Author) Other; Izquierdo, A (Author) Other; Jakubowska, A (Author) Other; James, PA (Author) Other; Janavicius, R (Author) Other; John, EM (Author) Other; Joseph, V (Author) Other; Karlan, BY (Author) Other; Kast, K (Author) Other; Koudijs, M (Author) Other; Kruse, TA (Author) Other; Kwong, A (Author) Other; Laitman, Y (Author) Other; Lasset, C (Author) Other; Lazaro, C (Author) Other; Lester, J (Author) Other; Lesueur, F (Author) Other; Liljegren, A (Author) Other; Loud, JT (Author) Other; Lubinski, J (Author) Other; Mai, PL (Author) Other; Manoukian, S (Author) Other; Mari, V (Author) Other; Mebirouk, N (Author) Other; Meijers Heijboer, HEJ (Author) Other; Meindl, A (Author) Other; Mensenkamp, AR (Author) Other; Miller, A (Author) Other; Montagna, M (Author) Other; Mouret Fourme, E (Author) Other; Mukherjee, S (Author) Other; Mulligan, AM (Author) Other; Nathanson, KL (Author) Other; Neuhausen, SL (Author) Other; Nevanlinna, H (Author) Other; Niederacher, D (Author) Other; Nielsen, FC (Author) Other; Nikitina Zake, L (Author) Other; Nogues, C (Author) Other; Olah, E (Author) Other; Olopade, OI (Author) Other; Ong, KR (Author) Other; O'Shaughnessy Kirwan, A (Author) Other; Osorio, A (Author) Other; Ott, CE (Author) Other; Papi, L (Author) Other; Park, SK (Author) Other; Parsons, MT (Author) Other; Pedersen, IS (Author) Other; Peissel, B (Author) Other; Peixoto, A (Author) Other; Peterlongo, P (Author) Other; Pfeiler, G (Author) Other; Phillips, KA (Author) Other; Prajzendanc, K (Author) Other; Pujana, MA (Author) Other; Radice, P (Author) Other; Ramser, J (Author) Other; Ramus, SJ (Author) Other; Rantala, J (Author) Other; Rennert, G (Author) Other; Risch, HA (Author) Other; Robson, M (Author) Other; Ronlund, K (Author) Other; Salani, R (Author) Other; Schuster, H (Author) Other; Senter, L (Author) Other; Shah, PD (Author) Other; Sharma, P (Author) Other; Side, LE (Author) Other; Singer, CF (Author) Other; Slavin, TP (Author) Other; Soucy, P (Author) Other; Southey, MC (Author) Other; Spurdle, AB (Author) Other; Steinemann, D (Author) Other; Steinsnyder, Z (Author) Other; Stoppa Lyonnet, D (Author) Other; Sutter, C (Author) Other; Tan, YY (Author) Other; Manuel R Teixeira (Author) ICBAS; Teo, SH (Author) Other; Thull, DL (Author) Other; Tischkowitz, M (Author) Other; Tognazzo, S (Author) Other; Toland, AE (Author) Other; Trainer, AH (Author) Other; Tung, N (Author) Other; van Engelen, K (Author) Other; van Rensburg, EJ (Author) Other; Vega, A (Author) Other; Vierstraete, J (Author) Other; Wagner, G (Author) Other; Walker, L (Author) Other; Wang Gohrke, S (Author) Other; Wappenschmidt, B (Author) Other; Weitzel, JN (Author) Other; Yadav, S (Author) Other; Yang, X (Author) Other; Yannoukakos, D (Author) Other; Zimbalatti, D (Author) Other; Offit, K (Author) Other; Thomassen, M (Author) Other; Couch, FJ (Author) Other; Schmutzler, RK (Author) Other; Simard, J (Author) Other; Easton, DF (Author) Other; Chenevix Trench, G (Author) Other; Antoniou, AC (Author) Other

Journal

Title: Genetics in Medicine

Vol. 22

Pages: 1653-1666

ISSN: 1098-3600

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 35 Citations

Scopus - 41 Citations

Other information

Authenticus ID: P-00S-TK2

DOI: 10.1038/s41436-020-0862-x

Abstract (EN): Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female 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 forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14