Interleukin-1B (IL-1B) polymorphisms and gastric mucosal levels of IL-1beta cytokine in Korean patients with gastric cancer.
Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1beta and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1beta cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1beta levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1beta production contributed to the development of intestinal-type GC in this Korean population.
Chang
Young-Woon
YW
Department of Gastroenterology, Kyung Hee University College of Medicine, Seoul, South Korea. cywgi@chollian.net
Jang
Jae-Young
JY
Kim
Nam-Hoon
NH
Lee
Jae Won
JW
Lee
Hyo Jung
HJ
Jung
Woon Won
WW
Dong
Seok-Ho
SH
Kim
Hyo-Jong
HJ
Kim
Byung-Ho
BH
Lee
Joung-Il
JI
Chang
Rin
R
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology*; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics* / Q000276:immunology*; D007723:Korea; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000276:immunology
D007375:Interleukin-1; D017472:Receptors, Interleukin-1