title: Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population.
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.
authors: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Oncology, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital, Shanghai, China.
authors: Fei
authors: F
authors: Zhou
authors: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Li-Xin
authors: LX
authors: Qiu
authors: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Lei
authors: L
authors: Cheng
authors: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Meng-Yun
authors: MY
authors: Wang
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Jin
authors: J
authors: Li
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors: Meng-Hong
authors: MH
authors: Sun
authors: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors: Ya-Jun
authors: YJ
authors: Yang
authors: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors: Jiu-Cun
authors: JC
authors: Wang
authors: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors: Li
authors: L
authors: Jin
authors: Department of Gastric Cancer and Soft Tissue Sarcoma Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors: Ya-Nong
authors: YN
authors: Wang
authors: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors: Qing-Yi
authors: QY
authors: Wei
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000276:immunology
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D012333:RNA, Messenger
keywords: gastric cancer; genetic variants; interleukin-17; molecular epidemiology; susceptibility