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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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  • J B A Crusius, Denmark
  • F Canzian, Denmark
  • G Capellá, Denmark
  • A S Peña, Denmark
  • G Pera, Denmark
  • N Sala, Denmark
  • A Agudo, Denmark
  • F Rico, Denmark
  • G Del Giudice, Denmark
  • D Palli, Denmark
  • M Plebani, Denmark
  • H Boeing, Denmark
  • H B Bueno-de-Mesquita, Denmark
  • F Carneiro, Denmark
  • V Pala, Denmark
  • V E Save, Denmark
  • P Vineis, Denmark
  • R Tumino, Denmark
  • S Panico, Denmark
  • G Berglund, Denmark
  • J Manjer, Denmark
  • R Stenling, Denmark
  • G Hallmans, Denmark
  • C Martinez, Denmark
  • M Dorronsoro, Denmark
  • A Barricarte, Denmark
  • C Navarro, Denmark
  • J R Quirós, Denmark
  • N Allen, Denmark
  • T J Key, Denmark
  • S Binghan, Denmark
  • C Caldas, Denmark
  • J Linseisen, Denmark
  • R Kaaks, Denmark
  • K Overvad
  • A Tjønneland, Denmark
  • F C Büchner, Denmark
  • P H M Peeters, Denmark
  • M E Numans, Denmark
  • F Clavel-Chapelon, Denmark
  • A Trichopoulou, Denmark
  • E Lund, Denmark
  • M Jenab, Denmark
  • S Rinaldi, Denmark
  • P Ferrari, Denmark
  • E Riboli, Denmark
  • C A González, Denmark
  • Department of Clinical Epidemiology
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.
Original languageEnglish
JournalAnnals of Oncology
Pages (from-to)1894-902
Number of pages8
Publication statusPublished - 2008

    Research areas

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

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