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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 publication

DOI

10.1158/1055-9965.epi-06-0072

Type

Journal article

Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Publication Date

12/2006

Volume

15

Pages

2427 - 2434

Addresses

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

Keywords

Humans, Tobacco, Adenocarcinoma, Stomach Neoplasms, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A2, Glutathione Transferase, Carcinogens, Case-Control Studies, Smoking, Genotype, Polymorphism, Genetic, Middle Aged, Europe, Female, Male, Nutritional Sciences, Polycyclic Aromatic Hydrocarbons