Fine-Mapping of IL16 Gene and Prostate Cancer Risk in African Americans

Background: Prostate cancer (Pca) is the most common type of cancer among men in the United States, and its incidence and mortality rates are disproportionate among ethnic groups. While genome-wide association studies of European descents have identified candidate loci associated with Pca risk, including a variant in IL16, replication studies in African Americans (AAs) have been inconsistent. Here we explore SNP variation in IL16 in AAs and test for association with Pca. Methods: Association tests were performed for 2,257 genotyped and imputed SNPs spanning IL16 in 605 AA Pca cases and controls from Washington, DC. Eleven of them were also genotyped in a replication population of 1,093 AAs from Chicago. We tested for allelic association adjusting for age, global and local West African ancestry. Results: Analyses of genotyped and imputed SNPs revealed that a cluster of IL16 SNPs were significantly associated with Pca risk. The strongest association was found at rs7175701 (P=9.8 x 10-8). In the Chicago population, another SNP (rs11556218) was associated with Pca risk (P=0.01). In the pooled analysis, we identified three independent loci within IL16 that were associated with Pca risk. SNP eQTL analyses revealed that rs7175701 is predicted to influence the expression of IL16 and other cancer related genes. Conclusion: Our study provides evidence that IL16 polymorphisms play a role in Pca susceptibility among AAs. Impact: Our findings are significant given that there has been limited focus on the role of IL16 genetic polymorphisms on Pca risk in AAs.