Interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms are not associated with premalignant gastric conditions: a combined haplotype analysis.
OBJECTIVE
Contradictory results have been reported about the role of interleukin-1B (IL1B) and IL1 receptor antagonist (IL1RN) alleles in gastric carcinogenesis. Here, IL1B and IL1RN polymorphisms were analyzed as genotypes and haplotypes in relation to the presence of atrophic gastritis (AG) and intestinal metaplasia in the stomach.


METHODS
Two hundred and seventy-eight patients (212 Caucasians and 66 Asians) aged 50 years and above, referred for upper endoscopy because of dyspeptic symptoms, were included in the study. Gastric biopsies were histologically assessed according to the updated Sydney classification. Genomic DNA was typed for polymorphisms at position -3737, -1464, -511, -31 for the IL1B gene and the allele 2 of IL1RN using restriction fragment length polymorphism of amplified PCR fragments and intron-spanning PCR analysis, respectively.


RESULTS
IL1B-1464-C/C genotype was associated with higher presence of AG in antrum of the stomach in Caucasians [odds ratio: 4.8 (95% confidence interval=1.7-14.3); P=0.028]. IL1B-1464-G/C genotype was associated with lower incidence of AG in corpus of the stomach in Asians [odds ratio: 0.7 (95% confidence interval=0.5-0.8); P=0.02]. IL1RN*2 allele was not linked with AG or intestinal metaplasia in all parts of the stomach both among Asians and Caucasians. Overall, data show that none of the major four IL1B polymorphisms (IL1B-3737C>T, -1464G>C, -511C>T, -31T>C) and the IL1RN*2 is individually, or in its haplotype configuration, linked to the presence of premalignant lesions in Caucasians.


CONCLUSIONS
The determination of these IL1-related loci does not have any predictive value for stratification of subgroups with respect to gastric cancer risk.
Kupcinskas
Limas
L
Department of Gastroenterology, Kaunas University of Medicine, Kaunas, Lithuania.
Wex
Thomas
T
Kupcinskas
Juozas
J
Leja
Marcis
M
Ivanauskas
Audrius
A
Jonaitis
Laimas Virgilijus
LV
Janciauskas
Dainius
D
Kiudelis
Gediminas
G
Funka
Konrads
K
Sudraba
Agnese
A
Chiu
Han-Mo
HM
Lin
Jaw-Town
JT
Malfertheiner
Peter
P
D000368:Aged; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D005260:Female; D005757:Gastritis, Atrophic / Q000208:ethnology / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000208:ethnology / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
C508585:IL1B protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta