Journal article

Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer

Burcu F Darst, Tokhir Dadaev, Ed Saunders, Xin Sheng, Peggy Wan, Loreall Pooler, Lucy Y Xia, Stephen Chanock, Sonja Berndt, Susan M Gapstur, Victoria Stevens, Demetrius Albanes, Stephanie J Weinstein, Vincent Gnanapragasam, Graham G Giles, Tu Nguyen-Dumont, Roger L Milne, Mark Pomerantz, Julie A Schmidt, Lorelei Mucci Show all

Journal of the National Cancer Institute | OXFORD UNIV PRESS INC | Published : 2021


BACKGROUND: There is an urgent need to identify factors specifically associated with aggressive prostate cancer (PCa) risk. We investigated whether rare pathogenic, likely pathogenic, or deleterious (P/LP/D) germline variants in DNA repair genes are associated with aggressive PCa risk in a case-case study of aggressive vs nonaggressive disease. METHODS: Participants were 5545 European-ancestry men, including 2775 nonaggressive and 2770 aggressive PCa cases, which included 467 metastatic cases (16.9%). Samples were assembled from 12 international studies and germline sequenced together. Rare (minor allele frequency < 0.01) P/LP/D variants were analyzed for 155 DNA repair genes. We compared si..

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Awarded by National Cancer Institute at the National Institutes of Health

Funding Acknowledgements

This work was supported by the National Cancer Institute at the National Institutes of Health grant (R01 CA196931) and an award from the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter. A full list of research support can be found in the Supplementary Materials.