Abstract B32: Evaluating genetic risk for prostate cancer among Japanese Americans and Latinos: The Multiethnic Cohort Study

Abstract

Abstract Prostate cancer displays dramatic differences in incidence rates across racial/ethnic groups. The genetic basis of prostate cancer may depend in part on race/ethnicity, which may partially account for the variability in prostate cancer rates across racial/ethnic groups. To search for novel risk variants for prostate cancer, within the Multiethnic Cohort Study we conducted a genome-wide association study of men of Japanese and Latino ancestry, two populations that have a lower burden of this disease. In addition, we tested established risk variants for prostate cancer and utilized these variants to develop genetic risk models of prostate cancer. For Japanese Americans (case/controls=1,033/1042), we identified 69 SNPs associated with prostate cancer risk at P < 1.0×10-4 outside of known risk regions. The most notable association was seen with rs1093117 at chromosome 2 (P=1.23×0-7). For 57 of the established risk variants for prostate cancer, 20 variants were significantly associated with prostate cancer in Japanese Americans. The cumulative effect of these risk alleles resulted in a 12% increased risk of disease for each additional allele (P=2.08×10-25), with Japanese American men in the top quartile of the risk allele distribution having a 3.2-fold increased risk of prostate cancer compared to those in the lowest quartile (P = 8.47×10-20). For Latinos (cases/controls=1,043/1,057), outside of known risk regions, 56 SNPs were associated with prostate cancer risk at P < 1.0×10-4 and rs4240731 at chromosome 12 was most strongly associated with disease (P = 2.60×10-6). For the 57 risk variants for prostate cancer, 19 variants were significantly associated with disease in Latinos. The cumulative effect of prostate cancer risk alleles resulted in a 9% increased risk of prostate cancer for each additional risk allele (P=2.67×10-6) and those in the highest risk quartile had a 2.7-fold increased risk of prostate cancer in comparison to men in the lowest risk quartile (P=1.55×10-13). In summary, our findings suggest established risk variants for prostate cancer significantly contribute to disease susceptibility and future work will examine replication of genome-wide association findings in independent panels of Japanese and Latino men. Citation Format: Iona C. Cheng, Daniel O. Stram, Laurence N. Kolonel, Brian E. Henderson, Loïc Le Marchand, Christopher A. Haiman, Gary K. Chen, Jing He, Peggy Wan, Xin Sheng, Loreall C. Pooler, Lynne R. Wilkens, Kristine R. Monroe. Evaluating genetic risk for prostate cancer among Japanese Americans and Latinos: The Multiethnic Cohort Study [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B32.