Advanced

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

Capella, Gabriel; Pera, Guillem; Sala, Nuria; Agudo, Antonio; Rico, Francisco; Del Giudicce, Giuseppe; Plebani, Mario; Palli, Domenico; Boeing, Heiner and Bueno-de-Mesquita, H. Bas, et al. (2008) In International Journal of Epidemiology 37(6). p.1316-1325
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... (More)
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) 1.023.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR 2.0; 95 CI 1.093.65) and K751Q alleles (OR 1.82; 95 CI 1.013.30) and XRCC1 R399Q (OR 1.69; 95 CI 1.022.79) 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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Epidemiology
volume
37
issue
6
pages
1316 - 1325
publisher
Oxford University Press
external identifiers
  • wos:000261461700020
  • scopus:57349167220
ISSN
1464-3685
DOI
10.1093/ije/dyn145
language
English
LU publication?
yes
id
07c5c9b1-679f-470e-b849-10fbef10cd3f (old id 1305561)
date added to LUP
2009-03-23 13:35:15
date last changed
2017-07-23 03:50:41
@article{07c5c9b1-679f-470e-b849-10fbef10cd3f,
  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) 1.023.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR 2.0; 95 CI 1.093.65) and K751Q alleles (OR 1.82; 95 CI 1.013.30) and XRCC1 R399Q (OR 1.69; 95 CI 1.022.79) 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.},
  author       = {Capella, Gabriel and Pera, Guillem and Sala, Nuria and Agudo, Antonio and Rico, Francisco and Del Giudicce, Giuseppe and Plebani, Mario and Palli, Domenico and Boeing, Heiner and Bueno-de-Mesquita, H. Bas and Carneiro, Fatima and Berrino, Franco and Vineis, Paolo and Tumino, Rosario and Panico, Salvatore and Berglund, Göran and Simán, Henrik and Nyren, Olof and Hallmans, Goran and Martinez, Carmen and Dorronsoro, Miren and Barricarte, Aurelio and Navarro, Carmen and Quiros, Jose R. and Allen, Naomi and Key, Tim and Bingham, Sheila and Caldas, Carlos and Linseisen, Jakob and Nagel, Gabriele and Overvad, Kim and Tjonneland, Anne and Boshuizen, Hendriek C. and Peeters, Petra H. M. and Numans, Mattijs E. and Clavel-Chapelon, Francoise and Trichopoulou, Antonia and Lund, Eiliv and Jenab, Mazda and Kaaks, Rudolf and Riboli, Elio and Gonzalez, Carlos A.},
  issn         = {1464-3685},
  language     = {eng},
  number       = {6},
  pages        = {1316--1325},
  publisher    = {Oxford University Press},
  series       = {International Journal of Epidemiology},
  title        = {DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study},
  url          = {http://dx.doi.org/10.1093/ije/dyn145},
  volume       = {37},
  year         = {2008},
}