Association of Family History and Polygenic Risk Scores With Prostate Cancer in Africa.

Abstract

African ancestry and family history (FHx) of prostate cancer (CaP) are among the few established CaP risk factors. Few studies have evaluated the association of FHx of CaP with the risk of this disease in African men. Using the Men of African Descent and Carcinoma of the Prostate (MADCaP) network, we evaluated the association of self-reported FHx of CaP in fathers and brothers in a case-control study of 2,505 prostate cancer cases and 2,222 age-matched controls ascertained from seven centers across Africa. We compared the association of FHx and a 451-SNP polygenic risk score (PRS). Compared with controls, CaP cases had a higher proportion of fathers and/or brothers with a history of CaP overall, as well as in men age <60 or ≥60 years, and in those with/without aggressive CaP (<i>P</i> < .001). A CaP diagnosis in fathers was associated with an odds ratio (OR) of 3.90 (95% CI, 2.66 to 5.72), 3.13 (95% CI, 2.02 to 4.86) in brothers, and 3.41 (95% CI, 2.51 to 4.64) in fathers and/or brothers. A one-unit PRS change was associated with an OR of 1.92 (95% CI, 1.72 to 2.13). Estimates for the PRS effect did not change substantially when FHx was included in the model. FHx is a strong predictor of CaP in African men. PRS is also associated with CaP largely independently of FHx. FHx may not always be reliably reported in Africa but the magnitude of recall or reporting bias is unlikely to have negated the observed association.