Interleukin-6 gene −174G>C and −636G>C promoter polymorphisms and prostate cancer risk

Abstract

Prostate cancer (PCa) is one of the most commonly diagnosed internal malignancies affecting men. Due to the important roles of IL-6 in different physiological and pathophysiological processes, IL-6 polymorphisms may modulate PCa risk. IL-6 -174 G>C (rs 1800795, also designated -236 G>C) and -636 G>C (rs 1800796, also designated -572 G>C) promoter polymorphisms have been implicated in PCa susceptibility, albeit still controversial. A literature search using PubMed and Highwire databases was conducted, resulting in eight case-control studies concerning the IL-6 -174 G>C polymorphism (11,613 PCa cases and 13,992 controls) and four case-control publications regarding the IL-6 -636 G>C polymorphism (1,941 PCa cases and 3,357 controls). In order to derive a more precise estimation, a meta-analysis based upon these selected case-control studies was performed. There was no significant association between IL-6 -174 G>C polymorphism and PCa increased risk. Nevertheless, the presence of allele C and the CC genotype were statistically significantly associated with decreased PCa risk in the overall analysis for IL-6 -636 G>C polymorphism. Additional studies in larger samples and analyses of functional repercussions of these SNPs in prostate tumor cells are necessary to validate these findings.

Association of interleukin-6 (-174 G/C) polymorphism with the prostate cancer risk: A meta-analysis

“…However, the present study suggested that there was a slightly significant association between the IL-6 (-174 G/C) polymorphism and prostate risk in African-American patients under the homozygote and recessive models (CC vs. GG: OR, 3.43; 95% CI, 1.01-11.71; P=0.049; and CC vs. GG/GC: OR, 3.51; 95% CI, 1.04-11.82; P=0.042, respectively), which contradicts the results of the Magalhaes et al (41) meta-analysis. In addition, no significant associations were found in Asians and Caucasians, which is consistent with the Magalhaes et al (41) and Zhang et al (42) studies, suggesting that ancestral genetic factors in different populations may have an impact on prostate cancer susceptibility. Additionally, the removal of the Mandal et al (32) study from the present meta-analysis showed that no significant association was found between the IL-6 (-174 G/C) polymorphism and the risk of prostate cancer in African-American patients under the homozygote (OR, 2.67; 95% CI, 0.69-10.36; P=0.17) and recessive models (OR, 2.64; 95% CI, 0.70-9.98; P=0.15).…”

“…The results suggested that no significant association was found in the population of Han people in the Hubei region, which was also identified in Caucasian patients (36). Additionally, two meta-analyses (41,42) based on studies published 4-10 years ago also held the same conclusion. However, a recent study published in January 2014 by Mandal et al (32) suggested that the GG genotype may be associated with an increased risk of prostate cancer in Caucasian subjects, whereas the CC genotype was associated with an increased risk in the African-American subjects.…”

Role of interleukin-6 gene polymorphisms in the development of prostate cancer

“…The authors of several previous studies have reported an association between IL-6 gene polymorphisms and prostate cancer risk, but the results are inconsistent (Bao et al, 2008;Magalhães et al, 2013;Mandić et al, 2013;Mandal et al, 2014;Yang et al, 2014). Mandal et al (2014) conducted a study in Caucasian subjects and found that the GG genotype of IL-6-174G>C was associated with increased risk of prostate cancer.…”

“…Mandić et al (2013) reported that IL-6-174G>C gene polymorphisms influence susceptibility to prostate cancer. However, some studies have produced inconsistent results; Magalhães et al (2013) conducted a case-control study to assess the role of IL-6-174G>C and IL-6-636G>C in the development of prostate cancer, and found no significant association between the IL-6-174G>C polymorphism and increased risk of prostate cancer. Bao et al (2008) reported that the GG+CG genotype of IL-6-174G>C was correlated with increased risk of prostate cancer compared with the CC genotype.…”

“…Therefore, this cytokine could contribute to the initiation, development, and metastasis of prostate cancer. Several studies have shown an association between IL-6 gene polymorphisms and the risk of prostate cancer, but the results are inconclusive (Magalhães et al, 2013;Mandić et al, 2013;Mandal et al, 2014;Yang et al, 2014). In this study, we investigated the role of two functional polymorphisms, IL-6-174G>C (rs1800795) and IL-6-572C>G (rs1800796), in the development of prostate cancer.…”