Abstract 1305: A genome-wide association study of prostate cancer in Uganda

Abstract

The greater incidence of prostate cancer in men of African ancestry remains one of the most important unanswered health disparities globally. No established environmental/lifestyle risk factors have been identified, with the only established risk factors being age, race/ethnicity and family history, all of which implicate genetic susceptibility. GWAS have clearly validated the importance of genetic susceptibility in prostate cancer, with ~100 common risk loci identified to date which in aggregate explain 33% of the familial risk. Genetic studies in African ancestry populations have provided strong evidence for genetic factors in contributing to the greater incidence of prostate cancer in men of African ancestry. To further explore this hypothesis, we conducted a genome-wide association study (GWAS) of prostate cancer among Ugandan men. Specifically, we genotyped the Illumina OncoArray, which includes a 260K GWAS backbone, in 560 prostate cancer cases (119 with Gleason score ≥8) and 480 controls and tested the associations of 448,939 genotyped and 16,396,662 imputed variants with >1% frequency. The most statistically significant variants were observed at the 8q24 risk locus (rs72725854, OR=3.37, P=2.14x10-13). We also observed suggestive signals with 106 variants outside of known risk regions with p-values <10-5 and >10-7. Of the 104 known risk variants, 100 are polymorphic in Uganda men, of which, 66 (66%) had effects that were directionally consistent in their association with prostate cancer risk as previously reported and 8 (8%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs16901979 at 8q24 (OR=1.45, p=0.0001) and rs1512268 at 8p21.2 (OR=1.31, p=0.0087). In addition to these findings, we will also present the results from replication testing of the most significant associations from the GWAS in the Ghana Prostate GWAS Study and the African Ancestry Prostate Cancer Consortium, as well as provide a detailed comparison of polygenic risk models of the known prostate cancer variants between these two African populations, African Africans and men of European ancestry. Citation Format: Zhaohui Du, Alexander Lubmawa, Susan Gundell, Peggy Wan, Nalukenge Cissy, Muwanga Proscovia, Lutalo Moses, Nansereko Deborah, Ndaruhutse Olivia, Katuku Molly, Lubwama Alexander, Rosemary Nassanga, Benson Masaba, Sam Kaggwa, Dan Namuguzi, Vicky Kiddu, Asiimwe Luke, Kuteesa J, Dabanja M. Henry, David Conti, Christopher A. Haiman, Stephen Watya. A genome-wide association study of prostate cancer in Uganda [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1305. doi:10.1158/1538-7445.AM2017-1305