Abstract
Prostate cancer is the most common type of cancer among men in the United States, and its incidence and mortality rates are disproportionate among ethnic groups. Although genome-wide association studies of European descents have identified candidate loci associated with prostate cancer risk, including a variant in IL16, replication studies in African Americans (AA) have been inconsistent. Here we explore single-nucleotide polymorphism (SNP) variation in IL16 in AAs and test for association with prostate cancer. Association tests were conducted for 2,257 genotyped and imputed SNPs spanning IL16 in 605 AA prostate cancer cases and controls from Washington, D.C. 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. Analyses of genotyped and imputed SNPs revealed that a cluster of IL16 SNPs were significantly associated with prostate cancer risk. The strongest association was found at rs7175701 (P = 9.8 × 10(-8)). In the Chicago population, another SNP (rs11556218) was associated with prostate cancer risk (P = 0.01). In the pooled analysis, we identified three independent loci within IL16 that were associated with prostate cancer risk. SNP expression quantitative trait loci analyses revealed that rs7175701 is predicted to influence the expression of IL16 and other cancer-related genes. Our study provides evidence that IL16 polymorphisms play a role in prostate cancer susceptibility among AAs. Our findings are significant given that there has been limited focus on the role of IL16 genetic polymorphisms on prostate cancer risk in AAs.
Highlights
Prostate cancer is the most common type of cancer among men in the United States, and its disproportionately higher rate of incidence and mortality among African Americans (AA) are very likely due to a combination of genes and environmental factors
Genomewide association studies (GWAS) in men of European descents have identified candidate loci associated with high prostate cancer risk [1,2,3,4,5,6], the same locus tend not to Authors' Affiliations: 1Institute of Human Genetics, College of Medicine; 2Section of Hematology/Oncology, Department of Medicine; 3Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL; 4Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and 5Division of Urology, Department of Surgery, Howard University Hospital, Washington, DC
Given that currently available genomewide association studies (GWAS) panels vary in genome coverage across ethnic groups because of marker selection and linkage disequilibrium (LD) differences, the "exact" replication of index singlenucleotide polymorphism (SNP) identified in people of European descent is often problematic in populations with lower LD [12]
Summary
Prostate cancer is the most common type of cancer among men in the United States, and its disproportionately higher rate of incidence and mortality among African Americans (AA) are very likely due to a combination of genes and environmental factors. A single-nucleotide polymorphism (SNP) in IL16, rs4072111, was associated with prostate cancer aggressiveness in European Americans (EA; 1), but a subsequent study in AAs did not replicate the result [7]. Given that currently available GWAS panels vary in genome coverage across ethnic groups because of marker selection and linkage disequilibrium (LD) differences, the "exact" replication of index SNPs identified in people of European descent is often problematic in populations with lower LD [12]. Genome-wide association studies of European descents have identified candidate loci associated with prostate cancer risk, including a variant in IL16, replication studies in African Americans (AA) have been inconsistent. We explore singlenucleotide polymorphism (SNP) variation in IL16 in AAs and test for association with prostate cancer
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