Rare germline genetic variants and risk of aggressive prostate cancer

T. Nguyen-Dumont, Robert J. MacInnis, Jason A. Steen, Derrick Theys, Helen Tsimiklis, Fleur Hammet, Maryam Mahmoodi, Bernard J. Pope, Daniel J. Park, Khalid Mahmood, Gianluca Severi, Damien Bolton, Roger L. Milne, Graham G. Giles, Melissa C. Southey

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8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2142-2149
Number of pages8
JournalInternational Journal of Cancer
Issue number8
Publication statusPublished - 15 Oct 2020


  • aggressive prostate cancer
  • gene panel testing
  • germline genetic variants

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