Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer

Int J Cancer. 2010 Jul 1;127(1):86-92. doi: 10.1002/ijc.25027.

Abstract

Chronic inflammation is the hallmark of the pathogenesis of Helicobacter pylori-induced gastric cancer. Interleukin (IL)-17A and IL-17F are inflammatory cytokines expressed by a novel subset of CD4+ Th cells and play critical function in inflammation and probably in cancer. We conducted a case-control study including 1,010 gastric cancer patients and 800 healthy controls to assess the association between IL-17A G197A and IL-17F A7488G polymorphisms and risk of gastric cancer. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Logistic regression and Cox-proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features and survival. After adjusted for age and gender, IL-17F 7488GA and GG genotypes were associated with an increased risk of gastric cancer compared with AA genotype [OR 1.51, 95% confidence interval (CI): 1.22-1.87 for GA; OR 1.61, 95% CI: 1.03-2.51 for GG]. Further stratification analyses indicated that the effect of IL-17F 7488GA genotype was noteworthy in gastric cancer patients of noncardia, intestinal type, poorly and moderately differentiated, age older than 40, large tumor size and lymph node metastasis. IL-17A 197AG genotype was associated with increased risk of poorly differentiated, TNM I/II, age of 40-65-year subtypes of gastric cancer, but not with total gastric cancer risk (p = 0.098). No significant relationship was observed between polymorphisms and survival of gastric cancer patients. These findings suggest that polymorphism of IL-17F 7488 involved in susceptibility to gastric cancer, which also influenced certain subtypes according to clinicopathological features, whereas IL-17A 197 may be less relevant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • DNA Primers
  • Female
  • Genetic Predisposition to Disease*
  • Helicobacter Infections / complications
  • Humans
  • Interleukin-17 / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Proportional Hazards Models
  • Stomach Neoplasms / complications
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Survival Analysis

Substances

  • DNA Primers
  • IL17F protein, human
  • Interleukin-17