Citations 1
Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry
Hughley, Raymond W. , Matejcic, Marco , Song, Ziwei , Sheng, Xin , Wan, Peggy , Xia, Lucy , Hart, Steven N. , Yadav, Siddhartha , Lubmawa, Alexander, Kiddu, Vicky , Asiimwe, Frank , Amanya, Colline , Mutema, George , Job, Kuteesa , Ssebakumba, Mbaaga K. , Hamilton, Ann S. , Watya, Stephen , Haiman, Christopher A. , Hu, Chunling , Yadav, Siddhartha , Lubmawa, Alexander , Kiddu, Vicky , Asiimwe, Frank , Amanya, Colline , Mutema, George , Job, Kuteesa , Ssebakumba, Mbaaga K , Ingles, Sue A. , Hamilton, Ann S , Couch, Fergus J. , Watya, Stephen , Conti, David V , Darst, Burcu F , Haiman, Christopher A , Hart, Steven N , Hu, Chunling , Couch, Fergus J. , Conti, David V. , Darst, Burcu F.
Cancer Research Communications | November 28, 2023 | Volume: 3 | Issue: 12 | Pages: 2544-2550
Abstract Prostate cancer risk is influenced by rare and common germline variants. We examined the aggregate association of rare germline pathogenic/likely pathogenic/deleterious (P/LP/D) variants in ATM, BRCA2, PALB2, and NBN with a polygenic risk score (PRS) on prostate cancer risk among 1,796 prostate cancer cases (222 metastatic) and 1,424 controls of African ancestry. Relative to P/LP/D non-carriers at average genetic risk (33%–66% of PRS), men with low (0%–33%) and high (66%–100%) PRS had Odds Ratios (ORs) for overall prostate cancer of 2.08 [95% confidence interval (CI) = 0.58–7.49] and 18.06 (95% CI = 4.24–76.84) among P/LP/D carriers and 0.57 (95% CI = 0.46–0.71) and 3.02 (95% CI = 2.53–3.60) among non-carriers, respectively. The OR for metastatic prostate cancer was 2.73 (95% CI = 0.24–30.54) and 28.99 (95% CI = 4.39–191.43) among P/LP/D carriers and 0.54 (95% CI = 0.31–0.95) and 3.22 (95% CI = 2.20–4.73) among non-carriers, for men with low and high PRS, respectively. Lifetime absolute risks of overall prostate cancer increased with PRS (low to high) from 9.8% to 51.5% in P/LP/D carriers and 5.5% to 23.9% in non-carriers. Lifetime absolute risks of metastatic prostate cancer increased with PRS from 1.9% to 18.1% in P/LP/D carriers and 0.3% to 2.2% in non-carriers These findings suggest that assessment of prostate cancer risk for rare variant carriers should include PRS status. Significance: These findings highlight the importance of considering rare and common variants to comprehensively assess prostate cancer risk in men of African ancestry.