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: 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, Qing-Yi Wei
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 50 Pg. 82384-82395 (Dec 13 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27577072 (Publication Type: Comparative Study, Journal Article, Meta-Analysis)

Chemical References

• IL17A protein, human
• Interleukin-17
• RNA, Messenger

Topics

• Asian People (genetics)
• Case-Control Studies
• Cell Line, Tumor
• Chi-Square Distribution
• China
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Haplotypes
• Heterozygote
• Homozygote
• Humans
• Interleukin-17 (genetics)
• Linear Models
• Logistic Models
• Male
• Middle Aged
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Quantitative Trait Loci
• RNA, Messenger (genetics)
• Risk Assessment
• Risk Factors
• Stomach Neoplasms (ethnology, genetics, immunology)