Jones Dominique Z, Ragin Camille, Kidd Nayla C, Flores-Obando Rafael E, Jackson Maria, McFarlane-Anderson Norma, Tulloch-Reid Marshall, Kimbro Kevin S, Kidd Lacreis R
Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA.
Hered Cancer Clin Pract. 2013 Dec 23;11(1):19. doi: 10.1186/1897-4287-11-19.
Although case-control studies have evaluated the role of variant inflammatory-related loci in prostate cancer, their impact is virtually unknown among men of African descent. To address this, we evaluated the impact of inflammatory cytokine single nucleotide polymorphisms (SNPs) on prostate cancer risk for men of African descent.
Forty-four SNPs in inflammatory cytokine-associated genes were evaluated among 814 African-American and Jamaican men (279 prostate cancer cases and 535 controls) using Illumina's Golden gate genotyping system. Individual SNP effects were evaluated using logistic regression analysis.
Four SNPs were modestly associated with prostate cancer after adjusting for age. In the total population, inheritance of the IL1R2 rs11886877 AA, IL8RB rs11574752 AA, TNF rs1800629 GA + AA, and TNF rs673 GA genotypes modestly increased prostate cancer risk by 1.45 to 11.7-fold relative to the referent genotype. Among U.S. men, age-adjusted dominant, recessive and additive genetic models for the IL1R2 rs11886877 locus were linked to an increase in prostate cancer susceptibility. However, these main effects did not persist after adjusting for multiple hypothesis testing.
Our preliminary data does not strongly support the hypothesis that inflammatory-related sequence variants influence prostate cancer risk among men of African descent. However, further evaluation is needed to assess whether other variant inflammatory-related genes may contribute to prostate cancer risk and disease progression in larger and ethnically diverse multi-center studies.
尽管病例对照研究已评估了炎性相关基因变异在前列腺癌中的作用，但在非洲裔男性中其影响几乎未知。为解决这一问题，我们评估了炎性细胞因子单核苷酸多态性（SNP）对非洲裔男性前列腺癌风险的影响。
使用Illumina的金标准基因分型系统，在814名非裔美国人和牙买加男性（279例前列腺癌病例和535例对照）中评估了炎性细胞因子相关基因中的44个SNP。使用逻辑回归分析评估个体SNP效应。
校正年龄后，有4个SNP与前列腺癌存在适度关联。在总体人群中，相对于参照基因型，IL1R2 rs11886877 AA、IL8RB rs11574752 AA、TNF rs1800629 GA + AA和TNF rs673 GA基因型的遗传使前列腺癌风险适度增加了1.45至11.7倍。在美国男性中，IL1R2 rs11886877位点的年龄校正显性、隐性和加性遗传模型与前列腺癌易感性增加有关。然而，在进行多重假设检验校正后，这些主要效应并未持续存在。
我们的初步数据并不强烈支持炎性相关序列变异影响非洲裔男性前列腺癌风险这一假设。然而，需要进一步评估，以确定在更大规模且种族多样的多中心研究中，其他炎性相关基因变异是否可能影响前列腺癌风险和疾病进展。
