The impact of genetic variants in inflammatory-related genes on prostate cancer risk among men of African Descent: a case control study

Abstract

PurposeAlthough 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.MethodsForty-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.ResultsFour 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.ConclusionOur 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.

Association of tumor necrosis factor-α 308G/A polymorphism with urogenital cancer risk: a systematic review and meta-analysis

“…Kohaar et al (2007) demonstrated that a single-nucleotide polymorphism (SNP) at -308 (G/A) of the TNFα promoter increased the risk of HPV infection and development in cervical cancer in Indian women. Although many studies have been performed to investigate the associations between the TNF-α 308G/A polymorphism and urogenital cancers, the results of these studies are controversial (Wu, 2004;Nonomura et al, 2006;Danforth et al, 2008;Wang et al, 2011;Barbisan et al, 2012;Jones et al, 2013). In Wu et al study (2004), 126 healthy people and 96 patients with prostate cancer were examined and their results suggested that prostate cancer appears to be associated with the p53 gene codon 72 polymorphisms, but not with the TNF-α gene.…”

“…The TNF-α 308G/A polymorphism is a G/A polymorphism at nucleotide (nt) -308, and is associated with the development of several urogenital cancers, including prostate cancer (Zabaleta et al, 2008;Moore et al, 2009;Jones et al, 2013), cervical cancer (Singh, 2009;Zuo et al, 2011), bladder cancer (Jeong et al, 2004;Kim et al, 2005;Leibovici et al, 2005), and renal cell carcinoma (Jang et al, 2001). For example, Jeong et al (2004) studied 113 patients with bladder cancer and 109 healthy subjects and found that the genotype of the 308 nucleotide in the TNF-α promoter had a statistically significant effect on TNF-α production and was related to the bladder tumor grade.…”

“…There are 13 studies (Oh et al, 2000;McCarron et al, 2002;Wu, 2004;Jinchao, 2007;Danforth et al, 2008;Sáenz-López et al, 2008;Zabaleta et al, 2008;Kesarwani, 2009;Moore et al, 2009;Wang et al, 2009a;Zhang et al, 2010;Berhane et al, 2012;Jones et al, 2013) focusing on prostate cancer, 19 studies (Jang et al, 2001;Calhoun et al, 2002;Gostout et al, 2003;Stanczuk et al, 2003;Deshpande et al, 2005;Duarte et al, 2005;Govan, 2006;Kohaar et al, 2007;Singh, 2009;Wang et al, 2009b;Ivansson, 2010;Zu, 2010;Wang et al, 2011;Zuo et al, 2011;Badano et al, 2012;Barbisan et al, 2012;Hang and Xu, 2012;Wang et al, 2012;Sousa et al, 2014) on cervical cancer, 6 studies (Tsai et al, 2001;Jeong et al, 2004;Kim et al, 2005;Leibovici et al, 2005;Nonomura et al, 2006;Ahirwar et al, 2008) on bladder cancer, 1 study (Jang et al, 2001) on renal cell cancer, and 1 study (Wu, 2013) on urothelial carcinoma. Five articles (Stanczuk et al, 2003;…”

“…Badano et al (2012) thought that the presence of the high producer allele TNF-α-308 A was correlated with an increased risk of cervical cancer in a Posadas population. However, results from other studies remain controversial (Nonomura et al, 2006;Danforth et al, 2008;Wang et al, 2011;Barbisan et al, 2012;Jones et al, 2013). Owing to these conflicting results, we conducted this metaanalysis to provide a comprehensive assessment of the associations between the TNF-α 308G/A polymorphism and the risk of urogenital cancer.…”

Inflammation polymorphisms and prostate cancer risk in Jamaican men: Role of obesity/body size

“…Among the inflammatory factors, cytokines (interleukins and TNFs) and chemokines (CC, CXC, XCL, and C-X3-C), are known to play an important role in host response to infection, inflammatory process, tumor development and metastasis [Jones, et al 2013]. Studies suggest that single nucleotide polymorphisms (SNPs) in inflammatory related genes and altered expression play a role in development and survival of various cancers including PC [Chang, et al 2009].…”