Rare germline genetic variants and risk of aggressive prostate cancer

Menée aux Etats-Unis auprès de 787 patients atteints d'un cancer agressif de la prostate (score de Gleason supérieur ou égal à 8) et 769 patients atteints d'un cancer non-agressif de la prostate, cette étude analyse la prévalence de 26 variants génétiques constitutionnels potentiellement pathogènes dans la forme agressive de la maladie

Résumé en anglais

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 non-aggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with non-aggressive PrCa (two-tailed Fisher’s exact tests, P = 0.28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with non-aggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P = 0.004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P = 0.06, 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.