IJE Advance Access published online on July 19, 2008
International Journal of Epidemiology, doi:10.1093/ije/dyn145
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DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study
1Translational Research Laboratory, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain.
2Department of Epidemiology, IDIBELL- Catalan Institute of Oncology, Barcelona, Spain.
3Center for Molecular and Medical Genetics, IDIBELL- Institut de Recerca Oncològica, Barcelona, Spain.
4IRIS Research Centre, CHIRON Vaccines, Siena, Italy.
5Servizio di Medicina di Laboratorio, Azienda Ospedaliera di Padova, Italy.
6Molecular and Nutritional Epidemiology Unit, CSPO Scientific Institute of Tuscany, Florence, Italy.
7German Institute of Human Nutrition, Postdam-Rehbüke, Germany.
8Center for Information Technology and Methodology, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
9Institute of Pathology and Molecular Immunology of the University of Porto (IPATIMUP) and Medical Faculty/H.S. Joao, Porto, Portugal.
10Epidemiology Unit, Istituto Tuimori, Milan, Italy.
11University of Torino and Imperial College London, UK.
12Cancer Registry, Azienda Ospedaliera Civile MP, Arezzo, Ragusa, Italy.
13Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
14Malmö Diet and Cancer Study, Lund University, Malmö, Sweden.
15Department of Medical Biosciences, University of Umeå, Sweden.
16Department of Nutritional Research, University of Umeå, Sweden.
17Andalusian School of Public Health, Granada, Spain.
18Department of Public Health of Guipuzkoa, San Sebastian, Spain.
19Public Health Institute of Navarra, Pamplona, Spain.
20Epidemiology Department, Health Council of Murcia, Murcia, Spain.
21Public Health Directorate for Health and Social Services of Asturias, Oviedo, Spain.
22Epidemiology Unit, Cancer Research UK, University of Oxford, Oxford, UK.
23Medical Research Council Dunn Human Nutrition Unit, Cambridge, UK.
24Cancer Genomics Program, Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
25Unit of Human Nutrition and Cancer Prevention and Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany.
26Institute of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark.
27Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
28Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
29INSERM, U 521, Institut Gustave Roussy, Villejuif, France.
30Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece.
31Institute of Community Medicine, University of Tromsø, Tromsø, Norway.
32Unit of Nutrition and Cancer, International Agency for Research on Cancer, Lyon, France.
33E Riboli. Department of Epidemiology and Public Health, Imperial College, London, UK.
*Corresponding author. Translational Research Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain. E-mail: capella{at}iconcologia.net
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Abstract |
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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.
Keywords Gastric carcinoma, DNA repair, polymorphism, genetic susceptibility, H. pylori
Accepted 18 June 2008