Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population
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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
Ya-Nong Wang, email: firstname.lastname@example.org
Qing-Yi Wei, email: email@example.com
Keywords: interleukin-17, genetic variants, gastric cancer, susceptibility, molecular epidemiology
Received: April 20, 2016 Accepted: July 28, 2016 Published: August 25, 2016
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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