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Ann Oncol. 2008 Nov;19(11):1894-902. doi: 10.1093/annonc/mdn400. Epub 2008 Jul 14.

Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST).

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  • 1Laboratory of Immunogenetics, Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

BACKGROUND:

The relative contribution to gastric cancer (GC) risk of variants in genes that determine the inflammatory response remains mostly unknown and results from genotyping studies are inconsistent.

PATIENTS AND METHODS:

A nested case-control study within the prospective European Prospective Investigation into Cancer and Nutrition cohort was carried out, including 248 gastric adenocarcinomas and 770 matched controls. Twenty common polymorphisms at cytokine genes [interleukin (IL)1A, IL1B, IL1RN, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, lymphotoxin alpha and tumor necrosis factor (TNF)] were analyzed. Antibodies against Helicobacter pylori (Hp) and CagA were measured.

RESULTS:

IL1RN 2R/2R genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19-4.96] and allele IL1RN Ex5-35C were associated with an increased risk of Hp(+) non-cardia GC. IL8 -251AA genotype was associated with a decreased risk of Hp(+) non-cardia GC (OR 0.51; 95% CI 0.32-0.81), mainly of the intestinal type. These associations were not modified by CagA status. Carriers of IL1B -580C and TNF -487A alleles did not associate with an increased risk. A moderately increased risk of Hp(+) non-cardia GC for IL4R -29429T variant was observed (OR 1.74; 95% CI 1.15-2.63).

CONCLUSION:

This prospective study confirms the association of IL1RN polymorphisms with the risk of non-cardia GC and indicates that IL8 -251T>A may modify the risk for GC.

PMID:
18628242
[PubMed - indexed for MEDLINE]
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