Abstract
Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13- 1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.
Highlights
Cancer is currently a major public health burden worldwide, which results from complicated interactions between genetic and environmental factors (Hoeijmakers, 2001; Bredberg, 2011)
Among these 9 included articles, one article by Kutikhin et al investigated the role of IL-17A -197G>A polymorphism in predisposition to colorectal and gastric cancer, respectively (Kutikhin et al, 2014)
Seven studies were involved in gastric cancer, two were in colorectal cancer and the last one was involved in esophageal cancer
Summary
Cancer is currently a major public health burden worldwide, which results from complicated interactions between genetic and environmental factors (Hoeijmakers, 2001; Bredberg, 2011). Inflammation has been linked to the pathogenesis of tumors in up to 15% of human cancers (Kuper et al, 2000). There has been evidence that human predisposition to cancer could be influenced by single nucleotide polymorphisms (SNPs) located in genes encoding cytokines and their receptors, mostly in promoter regions (Bidwell et al, 1999). IL-17A plays a pro-inflammatory role by recruiting neutrophils and inducing other inflammatory molecules, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α) (Moseley et al, 2003; Kolls and Linden, 2004). It has been reported that IL-17A promoted angiogenesis via stimulating vascular endothelial growth factor (VEGF) production of cancer cells in colorectal carcinoma and was associated with poor prognosis (Liu et al, 2011). IL-17A has been proved to be associated with the prognosis of operable non-small cell lung cancer (NSCLC)
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