Oncotarget

Research Papers:

Associations of potentially functional variants in IL-6, JAKs and STAT3 with gastric cancer risk in an eastern Chinese population

Fei Zhou _, Lei Cheng, Li-Xin Qiu, Meng-Yun Wang, Jin Li, Meng-Hong Sun, Ya-Jun Yang, Jiu-Cun Wang, Li Jin, Ya-Nong Wang and Qing-Yi Wei

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Oncotarget. 2016; 7:28112-28123. https://doi.org/10.18632/oncotarget.8492

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Abstract

Fei Zhou1,2,3,*, Lei Cheng1,2,*, Li-Xin Qiu1,2, Meng-Yun Wang1,2, Jin Li2, Meng-Hong Sun4, Ya-Jun Yang5,6, Jiu-Cun Wang5,6, Li Jin5,6, Ya-Nong Wang7, Qing-Yi Wei1,8

1Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China

2Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

3Department of Oncology, Shanghai Jiaotong University Affiliated Shanghai First People’s Hospital, Shanghai 20080, China

4Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China

5Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China

6Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu 225300, China

7Department of Gastric Cancer & Soft Tissue Sarcoma Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China

8Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA

*These authors have contributed equally to this work

Correspondence to:

Ya-Nong Wang, e-mail: [email protected]

Qing-Yi Wei, e-mail: [email protected], [email protected]

Keywords: interleukin-6/JAK/STAT3, signaling pathway, genetic variate, gastric cancer, genetic susceptibility

Received: December 08, 2015    Accepted: March 14, 2016    Published: March 30, 2016

ABSTRACT

The interleukin-6 (IL-6)/JAK/STAT3 signaling pathway plays a central role in inflammation-mediated cancers, including gastric cancer (GCa). We evaluated associations between 10 potentially functional single nucleotide polymorphisms (SNPs) of four essential genes in the pathway and GCa risk in a study of 1,125 GCa cases and 1,221 cancer-free controls. We found that a significant higher GCa risk was associated with IL-6 rs2069837G variant genotypes [adjusted odds ratios (OR) = 1.33; 95% confidence interval (CI) = 1.12-1.59 for AG + GG vs. AA)] and JAK1 rs2230587A variant genotypes (adjusted OR = 1.20; 95% CI = 1.02-1.43 for GA + AA vs. GG). We also found that a significant decreased GCa risk was associated with STAT3 rs1053004G variant genotypes (adjusted OR = 0.84; 95% CI = 0.71-0.99 for AG + GG vs. AA). The combined analysis of IL-6 rs2069837G and JAK1 rs2230587A variant risk genotypes revealed that individuals with one-or-two risk genotypes exhibited an increased risk for GCa (adjusted OR = 1.34; 95% CI = 1.13-1.59). Genotypes and mRNA expression correlation analysis using the data from the HapMap 3 database provided further support for the observed risk associations. Larger studies are warranted to validate these findings.


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