title: DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study.
abstract: BACKGROUND
  The contribution of genetic variation in DNA repair genes to gastric cancer (GC) risk remains essentially unknown. The aim of this study was to explore the relative contribution of DNA repair gene polymorphisms to GC risk and severe chronic atrophic gastritis (SCAG). Method A nested case control study within the EPIC cohort was performed including 246 gastric adenocarcinomas and 1175 matched controls. Controls with SCAG (n = 91), as defined by low pepsinogen A (PGA) levels, and controls with no SCAG (n = 1061) were also compared. Twelve polymorphisms at DNA repair genes (MSH2, MLH1, XRCC1, OGG1 and ERCC2) and TP53 gene were analysed. Antibodies against Helicobacter pylori were measured.
  
  
  RESULTS
  No association was observed for any of these polymorphisms with stomach cancer risk. However, ERCC2 K751Q polymorphism was associated with an increased risk for non-cardial neoplasm [odds ratio (OR) = 1.78; 95% confidence interval (CI) 1.02-3.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR = 2.0; 95% CI 1.09-3.65) and K751Q alleles (OR = 1.82; 95% CI 1.01-3.30) and XRCC1 R399Q (OR = 1.69; 95% CI 1.02-2.79) allele were associated with an increased risk for SCAG.
  
  
  CONCLUSIONS
  Our study supports a role of ERCC2 in non-cardial GC but not in cardial cancer. A concordant result was observed for subjects with low PGA levels. XRCC1 allele was associated also with SCAG. This is the first prospective study suggesting that individual variation in DNA repair may be relevant for gastric carcinogenesis, a finding that will require further confirmation validation in larger independent studies.
authors.affiliation: Translational Research Laboratory, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. capella@iconcologia.net
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellá
authors.forename: Guillem
authors.initials: G
authors.lastname: Pera
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.forename: Francisco
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authors.lastname: Rico
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudicce
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Göran
authors.initials: G
authors.lastname: Berglund
authors.forename: Henrik
authors.initials: H
authors.lastname: Simán
authors.forename: Olof
authors.initials: O
authors.lastname: Nyrén
authors.forename: Goran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Carmen
authors.initials: C
authors.lastname: Martinez
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: José R
authors.initials: JR
authors.lastname: Quirós
authors.forename: Naomi
authors.initials: N
authors.lastname: Allen
authors.forename: Tim
authors.initials: T
authors.lastname: Key
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Gabriele
authors.initials: G
authors.lastname: Nagel
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.forename: Hendriek C
authors.initials: HC
authors.lastname: Boshuizen
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Mattijs E
authors.initials: ME
authors.lastname: Numans
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002299:Cardia / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D004260:DNA Repair / Q000235:genetics*; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D005757:Gastritis, Atrophic / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020116:Pepsinogen A / Q000097:blood; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers; D020116:Pepsinogen A; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human