Oncotarget

Research Papers:

Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population

Fei Zhou, Li-Xin Qiu, Lei Cheng, 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; 7:82384-82395. https://doi.org/10.18632/oncotarget.11616

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Abstract

Fei Zhou1,2,3, Li-Xin Qiu1,2, Lei Cheng1,2, 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, China

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

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

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

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

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

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

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

Correspondence to:

Ya-Nong Wang, email: wangyn1111@hotmail.com

Qing-Yi Wei, email: weiqingyi@yahoo.com

Keywords: interleukin-17, genetic variants, gastric cancer, susceptibility, molecular epidemiology

Received: April 20, 2016     Accepted: July 28, 2016     Published: August 25, 2016

ABSTRACT

Interleukin-17 plays a crucial role in inflammation-related carcinogenesis. We hypothesize that genetic variants in IL-17 are associated with gastric cancer (GCa) risk, and we genotyped five potentially functional single nucleotide polymorphisms (SNPs) (rs1974226 G > A, rs2275913 A > G, rs3819024 A > G, rs4711998 A > G, and rs8193036 C > T) of IL-17 in 1121 GCa patients and 1216 cancer-free controls in an eastern Chinese population. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Meta-analysis and genotype-mRNA expression correlation were performed to further validate positive associations. We found that an increased GCa risk was independently associated with rs1974226 (adjusted OR = 2.60, 95% CI = 1.27–5.32 for AA vs. GG + GA) and rs2275913 (adjusted OR = 1.33, 95% CI = 1.03–1.72 for GA + AA vs. GG), while a decreased GCa risk was independently associated with rs3819024 (adjusted OR = 0.72, 95% CI = 0.54–0.96 for GG vs. AA + AG). Additional meta-analyses confirmed the observed risk association with rs2275913. We also found that two IL-17 haplotypes (G-G-G-A-C) and (A-G-G-A-C) (in the order of rs1974226, rs2275913, rs3819024, rs4711998 and rs8193036) were associated with a reduced GCa risk (adjusted OR = 0.64, 95% CI = 0.46–0.89 and adjusted OR = 0.38, 95% CI = 0.17–0.81, respectively). However, the expression Quantitative Trait Locus (eQTL) analysis for the genotype-phenotype correlation did not find mRNA expression changes associated with either the genotypes. In conclusions, genetic variants of IL-17 are likely to be associated with risk of GCa, and additional larger studies with functional validation are needed to explore the molecular mechanisms underlying the observed associations.


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