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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.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.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).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.

Original publication

DOI

10.1093/annonc/mdn400

Type

Journal article

Journal

Annals of oncology : official journal of the European Society for Medical Oncology

Publication Date

11/2008

Volume

19

Pages

1894 - 1902

Addresses

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

Keywords

Humans, Adenocarcinoma, Stomach Neoplasms, Genetic Predisposition to Disease, Tumor Necrosis Factor-alpha, Interleukins, Cytokines, Case-Control Studies, Prospective Studies, Nutritional Status, Genotype, Haplotypes, Polymorphism, Genetic, Adult, Aged, Middle Aged, Europe, Female, Male, Lymphotoxin-alpha