Institute of Human Genetics, College of Medicine, School of Public Health, University of Illinois at Chicago, Chicago, IL 60607-4067, USA.
Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):2059-68. doi: 10.1158/1055-9965.EPI-12-0707. Epub 2012 Aug 24.
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.
前列腺癌是美国男性中最常见的癌症类型，其发病率和死亡率在不同种族群体中不成比例。尽管欧洲血统的全基因组关联研究已经确定了与前列腺癌风险相关的候选基因座，包括 IL16 中的变异，但在非裔美国人（AA）中的复制研究结果并不一致。在这里，我们研究了 AA 中 IL16 的单核苷酸多态性（SNP）变异，并检验了其与前列腺癌的关联。
我们对 605 例 AA 前列腺癌病例和对照者中跨越 IL16 的 2257 个已分型和推测的 SNP 进行了关联检验，这些个体来自华盛顿特区。其中 11 个 SNP 也在来自芝加哥的 1093 例 AA 复制群体中进行了分型。我们在调整年龄、全球和局部西非祖源的情况下，对等位基因关联进行了检验。
对已分型和推测的 SNP 进行分析表明，IL16 中存在 SNP 簇与前列腺癌风险显著相关。在 rs7175701 处发现了最强的关联（P=9.8×10(-8)）。在芝加哥人群中，另一个 SNP（rs11556218）与前列腺癌风险相关（P=0.01）。在合并分析中，我们在 IL16 内鉴定出了三个与前列腺癌风险相关的独立基因座。SNP 表达数量性状基因座分析表明，rs7175701 可影响 IL16 和其他癌症相关基因的表达。
我们的研究提供了证据，表明 IL16 多态性在 AA 中前列腺癌易感性中发挥作用。
鉴于在 AA 中，IL16 遗传多态性对前列腺癌风险的作用受到的关注有限，因此我们的研究结果意义重大。
