A causal role of genetically elevated circulating interleukin-10 in the development of digestive cancers evidence from mendelian randomization analysis based on 29,307 subjects

Recent studies have observed a high level of circulating interleukin-10 (IL-10) in patients with digestive cancers, yet whether elevated IL-10 is causally associated with digestive cancers so far remained unresolved. We therefore meta-analyzed available observational studies with Mendelian randomization method to explore this causal association by employing IL-10 gene 3 variants (-592C>A,-819C>T, and-1082A>G) as instruments. Data were available from 52 articles encompassing 29,307 subjects. Subgroup analysis by cancer type indicated that-1082A>G was associated with increased risk of gastric cancer (odds ratio [OR]=1.19; 95% confidence interval [CI]: 1.05-1.35; P=0.006), and the association was reinforced for intestinal type gastric cancer (OR=1.26; 95%CI: 1.09- 1.44; P=0.001). By ethnicity, risk estimate for-1082G allele carriers was increased by 21% for digestive cancers in East Asians (95%CI: 1.05-1.40; P=0.009). As for the genotype-phenotype association, carriers of-1082G allele had an overall 20.21 pg/mL higher IL-10 level than those with-1082AA genotype (P=0.023). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 was 1.14 (95%CI: 1.01-16.99) in gastric cancer. Our findings provided evidence for a causal role of genetically elevated IL-10 in the development of gastric cancer, especially in East Asians and for intestinal type gastric cancer.