title: Genetic variants in IL-6/JAK/STAT3 pathway and the risk of CRC.
abstract: Interleukin (IL)-6 and the downstream Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway have previously been reported to be important in the development of colorectal cancer (CRC), and several studies have shown the relationship between the polymorphisms of related genes in this pathway with the risk of CRC. However, the findings of these related studies are inconsistent. Moreover, there has no systematic review and meta-analysis to evaluate the relationship between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility. Hence, we conducted a meta-analysis to explore the relationship between polymorphisms in IL-6/JAK/STAT3 pathway genes and CRC risk. Eighteen eligible studies with a total of 13,795 CRC cases and 18,043 controls were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library databases for the period up to September 15, 2015. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were used to calculate the strength of the association. Our results indicated that IL-6 genetic variants in allele additive model (OR = 1.05, 95 % CI = 1.00, 1.09) and JAK2 genetic variants (OR = 1.40, 95 % CI = 1.15, 1.65) in genotype recessive model were significantly associated with CRC risk. Moreover, the pooled data revealed that IL-6 rs1800795 polymorphism significantly increased the risk of CRC in allele additive model in Europe (OR = 1.07, 95 % CI = 1.01, 1.14). In conclusion, the present findings indicate that IL-6 and JAK2 genetic variants are associated with the increased risk of CRC while STAT3 genetic variants not. We need more well-designed clinical studies covering more countries and population to definitively establish the association between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility.
authors.affiliation: Department of General Surgery, Wuxi Hospital of traditional Chinese Medicine, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, No. 8 Zhongnan West Road, Wuxi, 214000, People's Republic of China. wangshuwei890207@163.com.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Wuxi Hospital of traditional Chinese Medicine, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, No. 8 Zhongnan West Road, Wuxi, 214000, People's Republic of China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D053612:Janus Kinases / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017594:Publication Bias; D012306:Risk; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D053612:Janus Kinases
keywords: Colorectal cancer; Interleukin-6; Janus kinase; Meta-analysis; Polymorphisms; Risk; Signal transducer and activator of transcription