title: 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.
abstract: 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.
authors.affiliation: From the State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (WN); Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province (QP, TL, ZW, JZ, MT, LZ, CL, KQ); Department of Hepatobiliary Surgery, The Affiliated Hospital of Qinghai University, Xining, Qinghai (ZW, LZ); Department of Ultrasound Diagnostics, The First Affiliated Hospital of Xi'an Jiaotong University (MT); Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province (LZ); and Chinese Academy of Sciences Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics (MG), Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
authors.forename: Qing
authors.initials: Q
authors.lastname: Pang
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Wang
authors.forename: Jingyao
authors.initials: J
authors.lastname: Zhang
authors.forename: Minghui
authors.initials: M
authors.lastname: Tai
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Mingliang
authors.initials: M
authors.lastname: Gu
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Qu
mesh_terms: D004067:Digestive System Neoplasms / Q000097:blood / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D057182:Mendelian Randomization Analysis; D012044:Regression Analysis
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10