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

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.

• Authors: Xiaoqin Wu, Zhirong Zeng, Bin Chen, Jun Yu, Ling Xue, Yuantao Hao, Minhu Chen, Joseph J Y Sung, Pinjin Hu
• Journal: International journal of cancer (Int J Cancer) Vol. 127 Issue 1 Pg. 86-92 (Jul 01 2010) ISSN: 1097-0215 [Electronic] United States
• PMID: 19904747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, genetics, pathology)
• Survival Analysis