DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study

Gabriel Capellá, Guillem Pera, Núria Sala, Antonio Agudo, Francisco Rico, Giuseppe Del Giudicce, Mario Plebani, Domenico Palli, Heiner Boeing, H. Bas Bueno-de-Mesquita, Fátima Carneiro, Franco Berrino, Paolo Vineis, Rosario Tumino, Salvatore Panico, Göran Berglund, Henrik Simán, Olof Nyrén, Goran Hallmans, Carmen MartinezMiren Dorronsoro, Aurelio Barricarte, Carmen Navarro, José R. Quirós, Naomi Allen, Tim Key, Sheila Bingham, Carlos Caldas, Jakob Linseisen, Gabriele Nagel, Kim Overvad, Anne Tjonneland, Hendriek C. Boshuizen, Petra Hm Peeters, Mattijs E. Numans, Françoise Clavel-Chapelon, Antonia Trichopoulou, Eiliv Lund, Mazda Jenab, Rudolf Kaaks, Elio Riboli, Carlos A. González

Research output: Contribution to journalArticle

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1316-1325
Number of pages10
JournalInternational Journal of Epidemiology
Volume37
Issue number6
DOIs
Publication statusPublished - 2008

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Keywords

  • DNA repair
  • Gastric carcinoma
  • Genetic susceptibility
  • H. pylori
  • Polymorphism

ASJC Scopus subject areas

  • Epidemiology

Cite this

Capellá, G., Pera, G., Sala, N., Agudo, A., Rico, F., Del Giudicce, G., Plebani, M., Palli, D., Boeing, H., Bueno-de-Mesquita, H. B., Carneiro, F., Berrino, F., Vineis, P., Tumino, R., Panico, S., Berglund, G., Simán, H., Nyrén, O., Hallmans, G., ... González, C. A. (2008). DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study. International Journal of Epidemiology, 37(6), 1316-1325. https://doi.org/10.1093/ije/dyn145