Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin-1 beta on development of peptic ulcer and gastric cancer.
OBJECTIVE
In Western countries, polymorphism of pro-inflammatory cytokine genes is associated with the development of gastric cancer and duodenal ulcer. The aim of this study was to clarify the association of polymorphisms of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha with susceptibility to peptic ulcer diseases and gastric cancer in Japan.


METHODS
The IL-1beta-511/-31 and TNF-alpha-308/-857/-863/-1031 genotypes were determined in Helicobacter pylori-positive patients with gastritis only (n = 164), gastric ulcers (n = 110), duodenal ulcers (n = 94), or gastric cancers (n = 105), and in H. pylori-negative controls (n = 172).


RESULTS
Carriage of the alleles TNF-alpha-857 T (odd ratio [OR], 1.826; 95% confidence interval [CI], 1.097-3.039), TNF-alpha-863 A (OR, 1.788; 95% CI, 1.079-2.905) and TNF-alpha-1031 C (OR, 1.912; 95% CI, 1.152-3.171) was associated with increased risk for gastric ulcer development. Carriage of the alleles TNF-alpha-857 T (OR, 1.686; 95% CI, 1.003-2.832), TNF-alpha-863 A (OR, 1.863; 95% CI, 1.118-3.107) and TNF-alpha-1031 C (OR 2.074; 95% CI, 1.244-3.457) was also associated with increased risk of gastric cancer development. There was no relationship between the development of H. pylori-related diseases and polymorphisms of IL-1beta-511/-31 and TNF-alpha-308. The simultaneous carriage of three different high-producer alleles of TNF-alpha-857/-863/-1031 significantly increased the risk of gastric ulcer (OR, 6.57; 95% CI, 2.34-18.40) and gastric cancer (OR, 5.20; 95% CI, 1.83-14.78).


CONCLUSIONS
Polymorphisms in TNF-alpha rather than IL-1beta are associated with increased risk for gastric ulcers and gastric cancer in Japan. The simultaneous carriage of more than one high-producer allele of TNF-alpha further increased the risks for gastric ulcer and cancer.
Sugimoto
Mitsushige
M
First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan. mitsu@hama-med.ac.jp
Furuta
Takahisa
T
Shirai
Naohito
N
Nakamura
Akiko
A
Xiao
Fang
F
Kajimura
Masayoshi
M
Sugimura
Haruhiko
H
Hishida
Akira
A
D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D016480:Helicobacter pylori / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha