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Genetic variants in IL-6/JAK/STAT3 pathway and the risk of CRC

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Tumor Biology

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.

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Authors and Affiliations

  1. 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, China

    Shuwei Wang & Weidong Zhang

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  1. Shuwei Wang
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  2. Weidong Zhang
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Correspondence to Shuwei Wang.

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Supplementary table 1

Characteristics of included SNPs in IL-6/JAK/STAT3 pathway. (DOCX 35 kb)

Supplementary table 2

The quality assessment of included trials. (DOCX 36 kb)

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Wang, S., Zhang, W. Genetic variants in IL-6/JAK/STAT3 pathway and the risk of CRC. Tumor Biol. 37, 6561–6569 (2016). https://doi.org/10.1007/s13277-015-4529-1

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