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Rare germline genetic variants and risk of aggressive prostate cancer
Author(s) -
NguyenDumont Tú,
MacInnis Robert J.,
Steen Jason A.,
Theys Derrick,
Tsimiklis Helen,
Hammet Fleur,
Mahmoodi Maryam,
Pope Bernard J.,
Park Daniel J.,
Mahmood Khalid,
Severi Gianluca,
Bolton Damien,
Milne Roger L.,
Giles Graham G.,
Southey Melissa C.
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33024
Subject(s) - germline , prostate cancer , context (archaeology) , disease , oncology , genetic testing , genetics , medicine , germline mutation , cancer , gene , biology , mutation , paleontology
Few genetic risk factors have been demonstrated to be specifically associated with aggressive prostate cancer (PrCa). Here, we report a case‐case study of PrCa comparing the prevalence of germline pathogenic/likely pathogenic (P/LP) genetic variants in 787 men with aggressive disease and 769 with nonaggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with nonaggressive PrCa (two‐tailed Fisher's exact tests, P = .28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with nonaggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P = .004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P = .06, respectively. Our findings contribute to the extensive international effort to interpret the genetic variation identified in genes included on gene‐panel tests, for which there is currently an insufficient evidence‐base for clinical translation in the context of PrCa risk.