title: Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition.
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.
authors.affiliation: Unit of Epidemiology, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Av. Gran Via s/n km 2.7, 08907 Barcelona, Spain. a.agudo@iconcologia.net
authors.forename: Antonio
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authors.forename: Núria
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authors.forename: Guillem
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authors.lastname: Capellá
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authors.forename: Sheila
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authors.lastname: Bingham
authors.forename: Kay-Tee
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authors.lastname: Overvad
authors.forename: Anne
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authors.lastname: Tjonneland
authors.forename: Anja
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authors.lastname: Olsen
authors.forename: H Bas
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authors.forename: Hendriek C
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authors.lastname: Boshuizen
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authors.lastname: Peeters
authors.forename: Mattijs E
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authors.lastname: Numans
authors.forename: Françoise
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authors.lastname: Clavel-Chapelon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Antonia
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authors.lastname: Trichopoulou
authors.forename: Eiliv
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authors.lastname: Lund
authors.forename: Johan
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authors.forename: Mazda
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authors.lastname: Jenab
authors.forename: Pietro
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authors.lastname: Ferrari
authors.forename: Teresa
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authors.lastname: Norat
authors.forename: Elio
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authors.lastname: Riboli
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authors.initials: CA
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mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D002273:Carcinogens / Q000378:metabolism*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D052756:Nutritional Sciences; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012907:Smoking / Q000235:genetics*; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics
chemical_list: D002273:Carcinogens; D011084:Polycyclic Aromatic Hydrocarbons; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase