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-IB 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 Helicobacterpylori 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 - 511 CC, 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 - 3 1 TT, adjusted OR, 2.00; 95% Cl, 1.02-3.89 for - 511 CC), which was consistent with the biological effects of IL-1beta. When we used the haplotype analyses and assumed the IL-IB - 3 IT 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. (C) 2004 Elsevier Ireland Ltd. All rights reserved.