Interleukin-1B gene promoter variants are associated with an increased risk of gastric cancer in a Chinese population.
Studies suggest that IL-1beta (encoded by IL-1B gene) is a pro-inflammatory cytokine and potent inhibitor of gastric acid secretion, which is proposed as a key determinant in gastric carcinogenesis. Two potentially functional polymorphisms (C-31T and T-511C) in the IL-1B promoter were suggested to be correlated with alteration of Helicobacter pylori infection and IL-1beta expression and therefore may be associated with risk of gastric cancer. To test the hypothesis that these two polymorphisms are associated with gastric cancer risk, we performed a case-control study of 280 histologically confirmed gastric cancer patients and 258 age, sex frequency-matched cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that the risks (adjusted odds ratio [OR] and 95% confidence interval [CI]) associated with the IL-1B variant genotypes were 1.64 (95% CI, 1.01-2.66) for -31TT and 1.52 (95% CI, 0.91-2.54) for -511CC, respectively, compared with their wild-type homozygotes. The risks were significantly more evident in individuals with H. pylori infection (adjusted OR, 2.14; 95% CI, 1.13-4.06 for -31TT; adjusted OR, 2.00; 95% CI, 1.02-3.89 for -511CC), which was consistent with the biological effects of IL-1beta. When we used the haplotype analyses and assumed the IL-1B -31T and -511C as risk alleles, no synergistic effect was found between these two loci. These findings indicate that these two IL-1B promoter variants may contribute to the risk of developing gastric cancer in the Chinese population, especially in individuals with H. pylori infection.
Yang
Jie
J
Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, 140 Hanzhong Road, Nanjing 210029, China.
Hu
Zhibin
Z
Xu
Yaochu
Y
Shen
Jin
J
Niu
Juyin
J
Hu
Xu
X
Guo
Jiantao
J
Wei
Qingyi
Q
Wang
Xinru
X
Shen
Hongbing
H
D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D053583:Interleukin-1beta; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics*
D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; C052994:interleukin-1beta (163-171)