Details

Autor(en) / Beteiligte

• 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
• Milne, Roger L.
• Giles, Graham G.
• Southey, Melissa C.

Titel

Rare germline genetic variants and risk of aggressive prostate cancer

Ist Teil von

• International journal of cancer, 2020-10, Vol.147 (8), p.2142-2149

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. What's new? Most studies on prostate cancer (PrCa) have searched for inherited genetic variants that predispose men to overall PrCa risk. This study compares the prevalence of germline pathogenic genetic variants in men with aggressive and non‐aggressive PrCa. The results confirm that germline gene panel testing allows the identification of men who carry BRCA2 pathogenic variants with increased risk of aggressive disease. Men with pathogenic variants in ATM were also at increased risk of aggressive disease. The findings contribute to the interpretation of the genetic variation identified in gene‐panel tests and the evidence base for its clinical translation in the context of PrCa risk.