Abstract 5066: Generalizability of established prostate cancer risk variants in men of African ancestry

Abstract

Abstract Background: Genome-wide association studies have identified more than eighty risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be utilized widely in risk modeling. Methods: We examined 82 previously reported risk variants in 5,096 prostate cancer cases and 4,972 controls of African ancestry. Association testing was performed using logistic regression adjusted for age, study and global ancestry. Cumulative effects were assessed through a multi-SNP genetic risk score. Results: Among the 82 known risk alleles, 68 (83%) were positively associated with prostate cancer risk in men of African ancestry and 30 (37%) were minimally replicated at p<0.05, with the most statistically significant variants being rs6983561 (p=1.1×10-16) and rs13254738 (p=1.8×10-15) at 8q24, as well as rs10896449 at 11q13 (p=5.5×10-7). With ≥80% statistical power, 27 variants failed to replicate at p<0.05. An aggregate score comprised of 79 unlinked alleles was strongly and equally associated with overall prostate cancer risk (per-allele odds ratio (OR)=1.06; p=1.2×10-47) and aggressive prostate cancer risk (OR=1.06; p=1.2×10-22). Conclusions: The consistent directions of effect for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Some variants that failed to replicate may not be the best markers of prostate cancer risk for men of African ancestry, and thus further exploration of these loci through sequencing and fine-mapping is needed. Citation Format: Ying Han, Lisa B. Signorello, Sara S. Strom, Rick A. Kittles, Benjamin A. Rybicki, Janet L. Stanford, Phyllis J. Goodman, Sonja I. Berndt, John Carpten, Graham Casey, Lisa Chu, David V. Conti, Kristin A. Rand, Ryan Diver, Anselm JM Hennis, Esther M. John, Adam S. Kibel, Eric A. Klein, Suzanne Kolb, Loic Le Marchand, M Cristina Leske, Adam B. Murphy, Christine Neslund-Dudas, Jong Y. Park, Curtis A. Pettaway, Timothy R. Rebbeck, Susan M. Gapstur, Siqun Lilly Zheng, Suh-Yuh Wu, John S. Witte, Jianfeng Xu, William B. Isaacs, Sue A. Ingles, Ann W. Hsing, The PRACTICAL Consortium, The ELLIPSE GAME-ON Consortium, Douglas F. Easton, Rosalind A. Eeles, Fredrick R. Schumacher, Stephen J. Chanock, Barbara Nemesure, William J. Blot, Daniel O. Stram, Brian E. Henderson, Christopher A. Haiman. Generalizability of established prostate cancer risk variants in men of African ancestry. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5066. doi:10.1158/1538-7445.AM2014-5066