title: Allele 2 of the interleukin-1 receptor antagonist gene is associated with early gastric cancer.
abstract: OBJECTIVE
  In advanced gastric cancer (tumor stages T2-T4), associations with polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early-stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa or submucosa (stage T1), the role of host genetic susceptibility remains to be determined.
  
  
  METHODS
  Eighty-eight patients with early-stage gastric cancer (stage T1, 77 positive for Helicobacter pylori) and 145 controls were genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis factor alpha (TNF-A) gene. Statistical analysis was performed using the chi2 test and the Fisher's exact test, respectively.
  
  
  RESULTS
  The homozygous genotype IL-1RN*2/2 of the IL-RN gene was strongly associated with early-stage gastric cancer (P < .0001), whereas further associations with the IL-1 gene cluster were not observed. A weak association of the TNF-A-308A allele with the diffuse type of early-stage gastric cancer, and an association with a composite of two or three proinflammatory polymorphisms, which predispose to increased production of the proinflammatory cytokines IL-1beta and TNF-alpha, could also be demonstrated.
  
  
  CONCLUSIONS
  The genotype IL-1RN*2/2 seems to be associated with early-stage gastric cancer. As opposed to advanced-stage gastric cancer, further proinflammatory cytokine polymorphisms were not associated independently, but might act in combination and mirror early steps of gastric carcinogenesis in hosts colonized by Helicobacter pylori. However, these findings await confirmation in future trials and should be underscored by gene expression studies.
authors.affiliation: Medizinische Poliklinik, Chirurgische Klinik und Poliklinik, Klinikum der Universität München, Standort Innenstadt, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Helga-Paula
authors.initials: HP
authors.lastname: Török
authors.forename: Agnes
authors.initials: A
authors.lastname: Schneider
authors.forename: Günter
authors.initials: G
authors.lastname: Brünnler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kopp
authors.forename: Ekkehard D
authors.initials: ED
authors.lastname: Albert
authors.forename: Manfred
authors.initials: M
authors.lastname: Stolte
authors.forename: Christian
authors.initials: C
authors.lastname: Folwaczny
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D017472:Receptors, Interleukin-1