The Interleukin-6 –174G/C Polymorphism and Prostate Cancer Risk: A Systematic Review and Meta-Analysis

Abstract

Objective: This systematic review and meta-analysis was undertaken to integrate previous findings and summarize the effect size of the association of interleukin-6 (IL-6) genetic polymorphism –174G/C with susceptibility to prostate cancer (PCa). Methods: All eligible studies of IL-6 –174G/C polymorphism and PCa risk were collected from the following electronic databases: PubMed and the Cochrane Library, with the last report up to June 1, 2011. Statistical analyses were performed by Review Manage version 5.0 and Stata 10.0. Results: A total of 7 independent studies, including 9,959 cases and 12,361 controls, were identified. When all studies were pooled, we did not detect a significant association of –174G/C polymorphism with PCa risk. When stratifying for race, similar results were obtained; evidence of a significant relation was absent in both Caucasians and the mixed population. After stratifying the studies by study types, –174G/C polymorphism was significantly associated with PCa risk when examining the contrast of CC + GC versus GG (OR = 1.44, 95% CI = 1.05–1.98, p = 0.03) in cohort studies but not in case-control studies. Conclusions: Our review suggest that –174G/C polymorphism is associated with an increased PCa risk in two cohort studies from one article. Additional well-designed studies are warranted to validate these findings.

Interleukin-12 and Interleukin-6 Gene Polymorphisms and Risk of Bladder Cancer in the Iranian Population

“…Also, genomic analysis did not reveal a difference between bladder cancer patients and healthy controls in allelic frequency at the -174 position for IL-6 gene promoter. This result is compatible with the four met-analysis of IL-6 -174G>C polymorphism and cancer risk (Xu et al, 2011;Liu et al, 2012;Yu et al, 2012;Zhang et al, 2012). However, this null association could be due a lack of consideration for the potential role of the environment; in other words, the gene-environment interaction role in cancer risk, as mentioned by Liu RY et al (Liu et al, 2012).…”

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.…”

Interleukin-6 as a Therapeutic Target

“…A meta-analysis was recently performed to evaluate the association between the IL6 174GC genotype and susceptibility to prostate cancer with an increased risk observed in two cohort studies. Additional well-designed studies are needed to validate the role of IL6 genetic polymorphism in prostatic cancer risk (68).…”