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

ABSTRACT: PURPOSE: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. METHODS: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. RESULTS: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. CONCLUSION: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.

SUBMITTER: Jones DZ

PROVIDER: S-EPMC3929257 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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

Jones Dominique Z DZ Ragin Camille C Kidd Nayla C NC Flores-Obando Rafael E RE Jackson Maria M McFarlane-Anderson Norma N Tulloch-Reid Marshall M Kimbro Kevin S KS Kidd Lacreis R LR

Hereditary cancer in clinical practice 20131223 1

<h4>Purpose</h4>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.<h4>Methods</h4>Forty-four SNPs in inflammatory cytokine-associated genes were evaluated among 814 African-American and Jamaican men (279 prostate cancer ...[more]

PMID: 24359571

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Project description:BACKGROUND:Polymorphisms in glutathione S-transferase (GST) genes may influence response to oxidative stress and modify prostate cancer (PCA) susceptibility. These enzymes generally detoxify endogenous and exogenous agents, but also participate in the activation and inactivation of oxidative metabolites that may contribute to PCA development. Genetic variations within selected GST genes may influence PCA risk following exposure to carcinogen compounds found in cigarette smoke and decreased the ability to detoxify them. Thus, we evaluated the effects of polymorphic GSTs (M1, T1, and P1) alone and combined with cigarette smoking on PCA susceptibility. METHODS:In order to evaluate the effects of GST polymorphisms in relation to PCA risk, we used TaqMan allelic discrimination assays along with a multi-faceted statistical strategy involving conventional and advanced statistical methodologies (e.g., Multifactor Dimensionality Reduction and Interaction Graphs). Genetic profiles collected from 873 men of African-descent (208 cases and 665 controls) were utilized to systematically evaluate the single and joint modifying effects of GSTM1 and GSTT1 gene deletions, GSTP1 105 Val and cigarette smoking on PCA risk. RESULTS:We observed a moderately significant association between risk among men possessing at least one variant GSTP1 105 Val allele (OR = 1.56; 95%CI = 0.95-2.58; p = 0.049), which was confirmed by MDR permutation testing (p = 0.001). We did not observe any significant single gene effects among GSTM1 (OR = 1.08; 95%CI = 0.65-1.82; p = 0.718) and GSTT1 (OR = 1.15; 95%CI = 0.66-2.02; p = 0.622) on PCA risk among all subjects. Although the GSTM1-GSTP1 pairwise combination was selected as the best two factor LR and MDR models (p = 0.01), assessment of the hierarchical entropy graph suggested that the observed synergistic effect was primarily driven by the GSTP1 Val marker. Notably, the GSTM1-GSTP1 axis did not provide additional information gain when compared to either loci alone based on a hierarchical entropy algorithm and graph. Smoking status did not significantly modify the relationship between the GST SNPs and PCA. CONCLUSION:A moderately significant association was observed between PCA risk and men possessing at least one variant GSTP1 105 Val allele (p = 0.049) among men of African descent. We also observed a 2.1-fold increase in PCA risk associated with men possessing the GSTP1 (Val/Val) and GSTM1 (*1/*1 + *1/*0) alleles. MDR analysis validated these findings; detecting GSTP1 105 Val (p = 0.001) as the best single factor for predicting PCA risk. Our findings emphasize the importance of utilizing a combination of traditional and advanced statistical tools to identify and validate single gene and multi-locus interactions in relation to cancer susceptibility.

Dataset Information

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

Publications

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

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