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

• Published in: Medicine (Baltimore) Vol. 95; no. 7; p. e2799
• Main Authors: Niu, Wenquan, Pang, Qing, Lin, Ting, Wang, Zhixin, Zhang, Jingyao, Tai, Minghui, Zhang, Lingqiang, Zhang, Li, Gu, Mingliang, Liu, Chang, Qu, Kai
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health, Inc. All rights reserved 01.02.2016; Wolters Kluwer Health
• Subjects: Digestive System Neoplasms - blood; Digestive System Neoplasms - genetics; Humans; Interleukin-10 - blood; Interleukin-10 - genetics; Mendelian Randomization Analysis; Regression Analysis; Systematic Reviewand Meta-Analysis
• ISSN: 0025-7974; 1536-5964; 1536-5964
• DOI: 10.1097/MD.0000000000002799

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.