IL-6 −174G>C polymorphism and cancer risk: a meta-analysis involving 29,377 cases and 37,739 controls

Interleukin-6 (IL-6) is a multifunctional cytokine involved in different physiologic and pathophysiologic processes and plays important roles in the etiology of cancer. The −174G>C polymorphism of the IL-6 gene influences IL-6 transcription and has been implicated in cancer risk. However, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 29,377 cancer cases and 37,739 controls from 50 published case–control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between −174G>C polymorphism and cancer risk. Overall meta-analysis indicated that no association was found between −174G>C genotypes and cancer risk. However, the positive association was found in bladder cancer (OR = 4.33, 95% CI: 1.93–9.71 for CC vs. GC, OR = 2.81, 95% CI: 1.39–5.68 for CC vs. GG, and OR = 2.19, 95% CI: 1.32–3.64 for CC vs. GG/GC), and among Asians (OR = 2.08, 95% CI: 1.07–4.06 for CC vs. GG, and OR = 2.20, 95% CI: 1.02–4.74 for CC vs. GG/GC) and Africans (OR = 1.61, 95% CI: 1.07–2.42 for GC vs. GG). This meta-analysis showed the evidence that the −174G>C of the IL-6 gene was a low-penetrance susceptibility gene for bladder cancer. Further larger, perferably prospective studies are needed to confirm this relationship.