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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 publication

DOI

10.1093/ije/dyn145

Type

Journal article

Journal

International journal of epidemiology

Publication Date

12/2008

Volume

37

Pages

1316 - 1325

Addresses

Translational Research Laboratory, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. capella@iconcologia.net

Keywords

Cardia, Humans, Helicobacter pylori, Helicobacter Infections, Adenocarcinoma, Stomach Neoplasms, Gastritis, Atrophic, Chronic Disease, Genetic Predisposition to Disease, Pepsinogen A, Biological Markers, Antibodies, Bacterial, Odds Ratio, Risk, Case-Control Studies, Follow-Up Studies, Prospective Studies, DNA Repair, Gene Frequency, Polymorphism, Genetic, Genes, p53, Adult, Aged, Middle Aged, Europe, Female, Male, Xeroderma Pigmentosum Group D Protein