Rare germline genetic variants and risk of aggressive prostate cancer.

2020-10-15

Nguyen-Dumont, 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 M

Milne, Roger L

Giles, Graham G

Southey, Melissa C

aggressive Prostate cancer

gene panel testing

germline genetic variants

Journal Article

0000-0002-6313-9005

10.1002/ijc.33024

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.

link

International Journal of Cancer 2020; 147(8): 2142-2149

International Journal of Cancer