Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer.
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.
Wu
Xiaoqin
X
Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Zeng
Zhirong
Z
Chen
Bin
B
Yu
Jun
J
Xue
Ling
L
Hao
Yuantao
Y
Chen
Minhu
M
Sung
Joseph J Y
JJ
Hu
Pinjin
P
D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis
D017931:DNA Primers; C440021:IL17F protein, human; D020381:Interleukin-17