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

J. B A Crusius, F. Canzian, G. Capellá, A. S. Peña, G. Pera, N. Sala, A. Agudo, F. Rico, G. Del Giudice, D. Palli, M. Plebani, H. Boeing, H. B. Bueno-de-Mesquita, F. Carneiro, V. Pala, V. E. Save, P. Vineis, R. Tumino, S. Panico, G. BerglundJ. Manjer, R. Stenling, G. Hallmans, C. Martínez, M. Dorronsoro, A. Barricarte, C. Navarro, J. R. Quirós, N. Allen, T. J. Key, S. Binghan, C. Caldas, J. Linseisen, R. Kaaks, K. Overvad, A. Tjønneland, F. C. Büchner, P. H M Peeters, M. E. Numans, F. Clavel-Chapelon, A. Trichopoulou, E. Lund, M. Jenab, S. Rinaldi, P. Ferrari, E. Riboli, C. A. González

Research output: Contribution to journalArticlepeer-review

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 α 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.

Original languageEnglish
Pages (from-to)1894-1902
Number of pages9
JournalAnnals of Oncology
Volume19
Issue number11
DOIs
Publication statusPublished - 2008

Keywords

  • Cytokine genes
  • Gastric carcinoma
  • Polymorphisms
  • Severe chronic atrophic gastritis

ASJC Scopus subject areas

  • Oncology
  • Hematology

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