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Polymorphisms in Metabolic Genes Related to Tobacco Smoke and the Risk of Gastric Cancer in the European Prospective Investigation into Cancer and Nutrition

¹ Unit of Epidemiology and ² Laboratory of Translational Research, Institut d'Investigacio Biomedicale Bellvitge, Catalan Institute of Oncology and ³ Medical and Molecular Genetics Center, Institut d'Investigacio Biomedicale Bellvitge, Oncology Research Institute, Hospitalet de Llobregat, Barcelona, Spain; ⁴ Epidemiology Unit, Center for Study and Prevention of Cancer, Florence, Italy; ⁵ German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany; ⁶ Immunobiological Research Institute of Siena, Chiron SPA, Siena, Italy; ⁷ Institute of Molecular Pathology and Immunology, University of Porto and Medical Faculty, Porto, Portugal; ⁸ Department of Epidemiology, National Cancer Institute, Milan, Italy; ⁹ Unit of Cancer Epidemiology, University of Turin and Centro di Prevenzione Oncologica Piemonte, Turin, Italy; ¹⁰ Cancer Registry, Azienda Ospedaliera Civile-M.P. Arezzo, Ragusa, Italy; ¹¹ Department of Clinical and Experimental Medicine, Federico II University, Medical School, Naples, Italy; ¹² Malmö Diet and Cancer Study, Lund University, Malmö, Sweden; ¹³ Department of Medical Biosciences, Pathology and ¹⁴ Department of Public Health and Clinical Medicine, Nutritional Research, University of Umeå, Umeå, Sweden; ¹⁵ Andalusian School of Public Health, Granada, Spain; ¹⁶ Fundación Vasca de Innovación e Investigación Sanitarias, Sondika, Bizkaia, Spain; ¹⁷ Public Health Institute, Navarra, Spain; ¹⁸ Consejería de Sanidad y Consumo, Murcia, Spain; ¹⁹ Dirección General de Salud Pública, Consejería de Salud y Servicios Sanitarios, Asturias, Spain; ²⁰ Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, United Kingdom; ²¹ Medical Research Council Dunn Human Nutrition Unit, Cambridge, United Kingdom; ²² Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany; ²³ Department of Clinical Epidemiology, Aalborg Hospital and Aarhus University Hospital and Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark; ²⁴ Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; ²⁵ Centre for Nutrition and Health, National Institute for Public Health and the Environment; ²⁶ Centre for Information Technology and Methodology, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; ²⁷ Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands; ²⁸ Institut National de la Sante et de la Recherche Medicale, Equipe E3N, Institut Gustave Roussy, Villejuif, France; ²⁹ Department of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece; ³⁰ Institute of Community Medicine, University of Tromso, Tromso, Norway; ³¹ Pathology Department, Academic Medical Centre, Amsterdam, the Netherlands; ³² Unit of Nutrition and Cancer, IARC, Lyon, France; and ³³ Cancer Epidemiology and Prevention, Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom

Requests for reprints: Antonio Agudo, Unit of Epidemiology, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Av. Gran Via s/n km 2.7, 08907 Barcelona, Spain. Phone: 34-932607401; Fax: 34-932607787. E-mail: a.agudo{at}iconcologia.net

Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C>A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus –3859G>A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2427–34)

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