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

TitleDNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study.
Publication TypeJournal Article
Year of Publication2008
AuthorsCapellá, G, Pera, G, Sala, N, Agudo, A, Rico, F, Del Giudicce, G, Plebani, M, Palli, D, Boeing, H, H Bueno-de-Mesquita, B, Carneiro, F, Berrino, F, Vineis, P, Tumino, R, Panico, S, Berglund, G, Simán, H, Nyrén, O, Hallmans, G, Martinez, C, Dorronsoro, M, Barricarte, A, Navarro, C, Quirós, JR, Allen, N, Key, T, Bingham, S, Caldas, C, Linseisen, J, Nagel, G, Overvad, K, Tjonneland, A, Boshuizen, HC, Peeters, PHM, Numans, ME, Clavel-Chapelon, F, Trichopoulou, A, Lund, iv, E, Jenab, M, Kaaks, R, Riboli, E, González, CA
JournalInt J Epidemiol
Volume37
Issue6
Pagination1316-25
Date Published2008 Dec
ISSN1464-3685
KeywordsAdenocarcinoma, Adult, Aged, Antibodies, Bacterial, Biological Markers, Cardia, Case-Control Studies, Chronic Disease, DNA Repair, Europe, Female, Follow-Up Studies, Gastritis, Atrophic, Gene Frequency, Genes, p53, Genetic Predisposition to Disease, Helicobacter Infections, Helicobacter pylori, Humans, Male, Middle Aged, Odds Ratio, Pepsinogen A, Polymorphism, Genetic, Prospective Studies, Risk, Stomach Neoplasms, Xeroderma Pigmentosum Group D Protein
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.

DOI10.1093/ije/dyn145
Alternate JournalInt J Epidemiol
Citation Key10.1093/ije/dyn145
PubMed ID18641418
Grant List / / British Heart Foundation / United Kingdom
/ / Cancer Research UK / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom