Abstract 1303: A genome-wide association study of prostate cancer in Latinos

Abstract

Abstract Recent studies estimate that individuals of African or Latin American ancestry represent less than 4% of samples analyzed to date in genome-wide association studies. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts in these populations. Here, we performed a genome-wide association study (GWAS) meta-analysis of prostate cancer in Latino men to search for risk loci that may be important in this population. We combined GWAS data for 1034 cases and 1046 controls genotyped with the Illumina 660 Beadarray with GWAS data for 1235 cases and 1053 controls genotyped with the Illumina Oncoarray as part of the ELLIPSE U19 GAME-ON Consortium. A total of ~11 million genotyped and imputed SNPs of ≥1% frequency were tested for association with prostate cancer risk in logistic regression models controlling for age, study and genetic ancestry. Genome-wide significant associations were observed with 24 variants all located at 8q24 (128.484-128.548), and which capture the first reported prostate cancer susceptibility locus in ‘region 1’ of 8q24. The most significant association genome-wide was with SNP rs7824776 (risk allele frequency, 0.35; OR=1.69, p=3.4x10-11). No novel genome-wide significant associations were noted outside of 8q24. We observed a high degree of generalizability of known prostate cancer risk loci, with 78 (76%) of the 103 known risk variants having effects that were directionally consistent in their association with prostate cancer risk as previously reported, of which 31 (30%) were statistically significant with p < 0.05. In addition to these findings from the largest GWAS of prostate cancer in Latinos conducted to date, we will also present the results investigating effect heterogeneity by local ancestry (i.e. proportion Native American vs. European). In addition, we will present a comparison of polygenic risk models between Latinos, African Africans and men of European ancestry that incorporate the known risk loci to better understand how genetic risk tracks with population differences in prostate cancer incidence. Citation Format: Hannah Hopp, Sue Ingles, Chad Huff, Xin Sheng, Brandi Weaver, Mariana Stern, Sara Strom, Ian Thompson, David Conti, Christopher A. Haiman. A genome-wide association study of prostate cancer in Latinos [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 1303. doi:10.1158/1538-7445.AM2017-1303