title: Circulating interleukin-6 and cancer: A meta-analysis using Mendelian randomization.
abstract: Interleukin-6 (IL-6) plays a contributory role in the progression and severity of many forms of cancer; it however remains unclear whether the relevance between circulating IL-6 and cancer is causal. We therefore meta-analyzed published articles in this regard using IL-6 gene -174G/C variant as an instrument. Seventy-eight and six articles were eligible for the association of -174G/C variant with cancer and circulating IL-6, respectively. Overall analyses failed to identify any significance between -174G/C and cancer risk. In Asians, carriers of the -174CC genotype had an 1.95-fold increased cancer risk compared with the -174GG genotype carriers (P = 0.009). By cancer type, significance was only attained for liver cancer with the -174C allele conferring a reduced risk under allelic (odds ratio or OR = 0.74; P = 0.001), homozygous genotypic (OR = 0.59; P = 0.029) and dominant (OR = 0.67; P = 0.004) models. Carriers of the -174CC genotype (weighted mean difference or WMD = -4.23 pg/mL; P < 0.001) and -174C allele (WMD = -3.43 pg/mL; P < 0.001) had circulating IL-6 reduced significantly compared with the non-carriers. In further Mendelian randomization analysis, a reduction of 1 pg/mL in circulating IL-6 was significantly associated with an 12% reduced risk of liver cancer. Long-term genetically-reduced circulating IL-6 might be causally associated with a lower risk of liver cancer.
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Mi
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wei
authors.affiliation: Institute of Anatomy, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Clinic Institute, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yang
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Pharmacology, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Molecular Imaging, Binzhou Medical University, Laishan District, Yantai, Shandong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D044466:Asian People; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D008113:Liver Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6