Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which were associated with non-high-grade serous ovarian cancer and MIGA1 which was associated with high-grade serous ovarian cancer. Further support for the association of HELB association comes from the observation that loss-of-function variants in HELB are associated with age at natural menopause and Mendelian randomisation analysis shows an association between ...
| Authors | Dicks, EM; Tyrer, JP; Ezquina, S; Jones, M; Baierl, J; Peng, PC; Diaz, M; Goode, E; Winham, SJ; Dörk, T; Gorp, TV; Fazio, A; Bowtell, DDL; Garsed, DW; Odunsi, K; Moysich, K; Pavanello, M; Fostira, F; Webb, PM; Soukupová, J; Cohen, PA; Sieh, W; Fortner, RT; Ricker, C; Karlan, B; Campbell, I; Brenton, JD; Ramus, SJ; Gayther, SA; Pharoah, PDP |
|---|---|
| Journal | European journal of human genetics : EJHG |
| Pages | |
| Volume | |
| Date | 12/03/2025 |
| Grant ID | P30 CA015083 | NCI NIH HHS [CA] (United States); P50 CA136393 | NCI NIH HHS [CA] (United States); R01 CA248288 | NCI NIH HHS [CA] (United States); PRCPJT-May21\100006 | Cancer Research UK (CRUK) |
| Funding Body | |
| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41431-025-01786-0 |