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

TitlePolymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition.
Publication TypeJournal Article
Year of Publication2006
AuthorsAgudo, A, Sala, N, Pera, G, Capellá, G, Berenguer, A, García, N, Palli, D, Boeing, H, del Giudice, G, Saieva, C, Carneiro, F, Berrino, F, Sacerdote, C, Tumino, R, Panico, S, Berglund, G, Simán, H, Stenling, R, Hallmans, G, Martinez, C, Bilbao, R, Barricarte, A, Navarro, C, Quirós, JR, Allen, N, Key, T, Bingham, S, Khaw, K-T, Linseisen, J, Nagel, G, Overvad, K, Tjonneland, A, Olsen, A, H Bueno-de-Mesquita, B, Boshuizen, HC, Peeters, PH, Numans, ME, Clavel-Chapelon, F, Boutron-Ruault, M-C, Trichopoulou, A, Lund, iv, E, Offerhaus, J, Jenab, M, Ferrari, P, Norat, T, Riboli, E, González, CA
JournalCancer Epidemiol Biomarkers Prev
Date Published2006 Dec
KeywordsAdenocarcinoma, Carcinogens, Case-Control Studies, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A2, Europe, Female, Genotype, Glutathione Transferase, Humans, Male, Middle Aged, Nutritional Sciences, Polycyclic Aromatic Hydrocarbons, Polymorphism, Genetic, Smoking, Stomach Neoplasms, Tobacco

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.

Alternate JournalCancer Epidemiol. Biomarkers Prev.
Citation Key10.1158/1055-9965.EPI-06-0072
PubMed ID17164366
Grant ListG0401527 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom