title: Circulating interleukin-10 levels and human papilloma virus and Epstein-Barr virus-associated cancers: evidence from a Mendelian randomization meta-analysis based on 11,170 subjects.
abstract: Recent studies have showed interleukin 10 (IL-10) is a critical cytokine that determines antiviral immune response and is related to virus-associated cancers. However, whether genetically elevated circulating IL-10 levels are associated with the risk of human papilloma virus and Epstein-Barr virus-associated cancers (HEACs) is still unclear. Mendelian randomization method was implemented to meta-analyze available observational studies by employing IL-10 three variants (-592C>A, -819C>T, and -1082A>G) as instruments. A total of 24 articles encompassing 11,170 subjects were ultimately eligible for the meta-analysis. Overall, there was a significant association between IL-10 promoter variant -1082A>G and HEACs under allelic and dominant models (both P<0.01). Subgroup analysis by cancer type indicated that the risk estimate of -1082A>G was significant for nasopharyngeal cancer under allelic, homozygous genotypic and dominant models (all P<0.001). Moreover by ethnicity, carriers of -1082G allele had a 74% increased risk for nasopharyngeal cancer in Asians under dominant model (odds ratio [OR] =1.737; 95% confidence interval [CI]: 1.280-2.358; P<0.001). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 levels was 1.14 (95% CI: 1.01-16.99) in HEACs. Our findings provided strong evidence for a critical role of genetically elevated circulating IL-10 levels in the development of HEACs, especially in Asian population and for nasopharyngeal cancer.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Qu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Pang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
keywords: Epstein-Barr virus; Mendelian randomization; human papilloma virus; interleukin-10; meta-analysis