Gastroenterology

Gastroenterology

Volume 121, Issue 4, October 2001, Pages 823-829
Gastroenterology

Alimentary Tract
Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma,☆☆

https://doi.org/10.1053/gast.2001.28000Get rights and content

Abstract

Background & Aims: Interleukin (IL)-1 gene cluster proinflammatory polymorphisms have been associated with development of gastric atrophy and with increased risk of gastric carcinoma. We aimed to determine the association between IL-1 loci polymorphisms and increased risk of gastric carcinoma in samples from a Portuguese population, and to find whether there was any relationship with the histologic types of gastric carcinoma. Methods: In a case-control study including 220 controls and 152 patients with gastric carcinoma (intestinal, 76; diffuse, 37; and atypical, 39), both the IL-1B–511 biallelic polymorphism and the IL-1RN penta-allelic variable number of tandem repeats were genotyped. Results: We found a significant association between the IL-1 polymorphisms and increased risk for tumor development in patients with intestinal-type gastric carcinoma. A trend towards an increased risk of tumor development was also observed in patients with diffuse-type gastric carcinoma. No significant relationship was observed in patients with atypical carcinoma. Carriers of IL-1B-511T and IL-1RN*2 homozygotes had increased risk for developing intestinal-type gastric carcinoma with odds ratios of 2.7 (95% confidence interval [CI], 1.5–4.9) and 3.1 (95% CI, 1.5–6.5), respectively. Statistical analysis showed an interaction between the 2 loci with the risk conferred by the IL-1B-511T allele substantially increased (odds ratio, 9.0; 95% CI, 3.5–23.0) in individuals homozygous for the IL-1RN*2 allele. Conclusions: Our results provide further support to the association between IL-1 gene cluster proinflammatory polymorphisms and increased risk of gastric carcinoma. Furthermore, we found evidence pointing to the existence of a synergistic interaction between the IL-1B and IL-1RN polymorphisms.

GASTROENTEROLOGY 2001;121:823-829

Section snippets

Tissue material

We evaluated, in a case-control study, the IL-1B-511 biallelic and IL-1RN penta-allelic variable number of tandem repeats (VNTR) polymorphisms. The study was performed in a control group of blood donors (n = 220) and in a series of patients with gastric carcinoma (n = 152). Both sample groups were collected in northern Portugal. In the control group, the average age was 38.3 ± 11.6 years (range, 19–61 years) and the male:female ratio was 1.6:1. In the gastric carcinoma group, the average age

IL-1B-511C/T

In the control population, the IL-1B-511C/T genotypes (Figure 1A) showed no evidence of deviation from Hardy–Weinberg equilibrium (P = 0.1; Table 1).

. Genotyping of the IL-1B-511C/T and IL-1RN VNTR polymorphisms. (A) PCR/SSCP analysis of the IL-1B-511C/T polymorphism showing the C/T, C/C, and T/T genotypes. (B) PCR/agarose gel electrophoresis analysis of the IL-1RN VNTR polymorphism illustrating the most common genotypes in our series (M, size marker; C−, negative control).

Comparison of genotype

Discussion

We assessed the association between the IL-1B-511C/T and IL-1RN VNTR polymorphisms and the risk of gastric carcinoma in a population from northern Portugal. In Portugal, the incidence and mortality rates of gastric carcinoma are among the highest in the world and in the north of the country it has been shown that H. pylori infects more than 80% of the asymptomatic adult population and more than 95% of relatives of patients with gastric carcinoma. In a population of distinct geographical

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    Address requests for reprints to: José Carlos Machado, IPATIMUP, Rua Roberto Frias, s/n, 4200 Porto, Portugal. e-mail: [email protected]; fax: (351) 225570799.

    ☆☆

    Supported by Fundação para a Ciência e a Tecnologia (FCT) (grant 35374/99 Sapiens Proj99) and by Programa Operacional Ciência, Tecnologia e lnovação (POCTI) do Quadro Comunitário de Apoio (QCA) II.

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