Pathogenic Variants in Cancer Predisposition Genes and Prostate Cancer Risk in Men of African Ancestry

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dc.contributor.authorMatejcic, Marco
dc.contributor.authorLubmawa, Alexander
dc.contributor.authorKiddu, Vicky
dc.contributor.authorMasaba, Benon
dc.contributor.authorNamuguzi, Dan
dc.contributor.authorMutema, George
dc.contributor.authorKuteesa, Job
dc.contributor.authorDabanja, Henry M.
dc.contributor.authorWatya, Stephen
dc.date.accessioned2022-03-20T20:18:33Z
dc.date.available2022-03-20T20:18:33Z
dc.date.issued2020
dc.description.abstractIn studies of men of European ancestry, rare pathogenic variants in DNA repair pathway genes have been shown to be associated with risk of aggressive prostate cancer. The contribution of rare coding variation to prostate cancer risk in men of African ancestry has not been established. We sequenced a panel of 19 DNA repair and cancer predisposition genes in 2,453 African American and 1,151 Ugandan cases and controls with prostate cancer. Rare variants were classified as pathogenic or putatively functionally disruptive and examined in association with prostate cancer risk and disease aggressiveness in gene and pathway-level association analyses. Pathogenic variants were found in 75 of 2,098 cases (3.6%) and 31 of 1,481 controls (2.1%; odds ratio [OR], 1.82; 95% CI, 1.19 to 2.79; P = .0044), with the association being stronger for more aggressive disease phenotypes (OR, 3.10; 95% CI, 1.54 to 6.23; P = .0022). The highest risks for aggressive disease were observed with pathogenic variants in the ATM, BRCA2, PALB2, and NBN genes, with ORs ranging from approximately 4 to 15 in the combined study sample of African American and Ugandan men. Rare, nonpathogenic, nonsynonymous variants did not have a major impact on risk of overall prostate cancer or disease aggressiveness.Rare pathogenic variants in DNA repair genes have appreciable effects on risk of aggressive prostate cancer in men of African ancestry. These findings have potential implications for panel testing and risk stratification in this high-risk population.en_US
dc.identifier.citationMatejcic, Marco & Patel, Yesha & Lilyquist, Jenna & Hu, Chunling & Lee, Kun & Gnanaolivu, Rohan & Hart, Steven & Polley, Eric & Yadav, Siddhartha & Boddicker, Nicholas & Samara, Raed & Xia, Lucy & Sheng, X. & Lubmawa, Alexander & Kiddu, Vicky & Masaba, Benon & Namuguzi, Dan & Mutema, George & Kuteesa, Job & Haiman, Christopher. (2020). Pathogenic Variants in Cancer Predisposition Genes and Prostate Cancer Risk in Men of African Ancestry. JCO Precision Oncology. 4. 32-43. 10.1200/PO.19.00179.en_US
dc.identifier.urihttps://nru.uncst.go.ug/xmlui/handle/123456789/2834
dc.language.isoenen_US
dc.publisherJCO Precision Oncologyen_US
dc.titlePathogenic Variants in Cancer Predisposition Genes and Prostate Cancer Risk in Men of African Ancestryen_US
dc.typeArticleen_US
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