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

Research output: Contribution to journalArticle


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: IL1RN2R/2R genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19-4.96] and allele IL1RNEx5-35C 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.


  • J. B. A. Crusius
  • F. Canzian
  • G. Capella
  • A. S. Pena
  • 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
  • Göran Berglund
  • And 27 others
  • J. Manjer
  • R. Stenling
  • G. Hallmans
  • C. Martinez
  • M. Dorronsoro
  • A. Barricarte
  • C. Navarro
  • J. R. Quiros
  • N. Allen
  • T. J. Key
  • S. Binghan
  • C. Caldas
  • J. Linseisen
  • R. Kaaks
  • K. Overvad
  • A. Tjonneland
  • F. C. Buechner
  • P. H. M. Peeters
  • M. E. Numans
  • F. Clavel-Chapelon
  • A. Trichopoulou
  • E. Lund
  • M. Jenab
  • S. Rinaldi
  • P. Ferrari
  • E. Riboli
  • C. A. Gonzalez
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • cytokine genes, polymorphisms, atrophic gastritis, severe chronic, gastric carcinoma
Original languageEnglish
Pages (from-to)1894-1902
JournalAnnals of Oncology
Issue number11
StatePublished - 2008
Publication categoryResearch