Associations of interleukin-6 gene polymorphisms with cancer risk: Evidence based on 49,408 cancer cases and 61,790 controls

Many molecular epidemiologic studies have shown that interleukin-6 (IL-6) polymorphisms are significantly associated with susceptibility for various cancers. However, the conclusions of these studies are inconsistent. The purpose of the present study was to explore the association between three common IL-6 loci (rs1800795, rs1800796, and rs1800797) and the risk for various cancers. We systematically searched the PubMed, Web of Science, Wanfang and China national knowledge infrastructure (CNKI) databases for relevant publications and obtained 108 eligible studies, involving 49,408 cancer patients and 61,790 cancer-free controls. Odds ratio (OR), 95% confidence interval (CI), and false positive reporting probability (FPRP) were used to evaluate cancer risk. All statistical analyses were performed using the R software meta package. We observed a non-significant association between rs1800795 and overall cancer risk, while rs1800797 was found to have a false positive association with overall risk of cancer. Subgroup analyses of rs1800797 also suggested non-significant association and rs1800795 played a protective role in liver cancer. Rs1800796 was found to be associated with overall cancer risk, particularly in Asian patients and those with prostate cancer. These findings provide evidence that IL-6 polymorphisms may affect cancer risk.