Abstract
A good number of genome-wide association studies (GWAS), including meta-analyses, reported that single nucleotide polymorphisms (SNPs) of the IL-6 gene are significantly associated with various types of cancer risks, though some other studies reported insignificant association with cancers, in the literature. These contradictory results may be due to variations in sample sizes and/or deficiency of statistical modeling. Therefore, an attempt is made to provide a more comprehensive understanding of the association between the IL-6 gene SNPs (rs1800795, rs1800796, rs1800797) and different cancer risks, giving the weight on a large sample size, including different cancer types and appropriate statistical modeling with the meta-dataset. In order to attain a more reliable consensus decision about the association between the IL-6 gene polymorphisms and different cancer risks, in this study, we performed a multi-case statistical meta-analysis based on the collected information of 118 GWAS studies comprising of 50053 cases and 65204 control samples. Results from this Meta-analysis indicated a significant association (p-value < 0.05) of the IL-6 gene rs1800796 polymorphism with an overall increased cancer risk. The subgroup analysis data based on cancer types exhibited significant association (p-value < 0.05) of the rs1800795 polymorphism with an overall increased risk of cervical, liver and prostate cancers; the rs1800796 polymorphism with lung, prostate and stomach cancers; and the rs1800797 polymorphism with cervical cancer. The subgroup analysis of ethnicity data showed a significant association (p-value < 0.05) of an overall cancer risk with the rs1800795 polymorphism for the African and Asian populations, the rs1800796 polymorphism for the Asian only and the rs1800797 polymorphism in the African population. Comparative discussion showed that our multi-case meta-analyses received more support than any previously reported individual meta-analysis about the association between the IL-6 gene polymorphisms and cancer risks. Results from this study, more confidently showed that the IL-6 gene SNPs (rs1800795, rs1800796 and rs1800797) in humans are associated with increased cancer risks. Therefore, these three polymorphisms of the IL-6 gene have the potential to be evaluated as a population based rapid, low-cost PCR prognostic biomarkers for different types of cancers diagnosis and research.
Highlights
Cancer is a leading cause of death worldwide
The results computed through this study suggested that the IL-6 rs1800795 polymorphism is insignificantly associated with the overall cancer risk, but significantly reduced the risk of liver cancer under four genetic models (CC vs. GG; CC vs. CG + GG; CC + CG vs. GG; CG vs. CC + GG; C vs. G), which is in line with the previously reported multi-case meta-analysis in [130]
This single nucleotide polymorphisms (SNPs) showed significant association with the increasing risk of cervical and prostate cancers, where the results of cervical cancer are supported by the previous single-case meta-analysis in [123], but not with the multi-case meta-analysis in [130]
Summary
Cancer is a leading cause of death worldwide. According to the World Health Organization (WHO), 9.6 million deaths occurred in 2018 from 18.1 million cancer patients all over the globe. According to the recent literature reviews, it is very much evident that cancer is a multi-factorial progressive disorder that developed under the influence of genes and their interactions [2,3,4]. Interleukin-6 (IL-6) gene encodes a cytokine that functions in inflammation and has been reported in association with cancers in the literature for many years [3, 4]. The IL-6 rs1800795 (-174G/C) polymorphism is a significant predictor for susceptibility of prostate cancer and bone metastasis in northwest Iranian population [11]. We observed that the reported results varied across studies and remain inconclusive, which may be occurred due to the smaller sample size and different ethnic populations
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