Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition

Antonio Agudo, Núria Sala, Guillem Pera, Gabriel Capellá, Antonio Berenguer, Nadia García, Domenico Palli, Heiner Boeing, Giuseppe Del Giudice, Calogero Saieva, Fatima Carneiro, Franco Berrino, Carlotta Sacerdote, Rosario Tumino, Salvatore Panico, Göran Berglund, Henrik Simán, Roger Stenling, Göran Hallmans, Carmen MartínezRoberto Bilbao, Aurelio Barricarte, Carmen Navarro, José R. Quirós, Naomi Allen, Tim Key, Sheila Bingham, Kay Tee Khaw, Jakob Linseisen, Gabriele Nagel, Kim Overvad, Anne Tjonneland, Anja Olsen, H. Bas Bueno-De-Mesquita, Hendriek C. Boshuizen, Petra H. Peeters, Mattijs E. Numans, Françoise Clavel-Chapelon, Marie Christine Boutron-Ruault, Antonia Trichopoulou, Eiliv Lund, Johan Offerhaus, Mazda Jenab, Pietro Ferrari, Teresa Norat, Elio Riboli, Carlos A. González

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2427-2434
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume15
Issue number12
DOIs
Publication statusPublished - Dec 2006

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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