Agudo Antonio, Sala Núria, Pera Guillem, Capellá Gabriel, Berenguer Antonio, García Nadia, Palli Domenico, Boeing Heiner, Del Giudice Giuseppe, Saieva Calogero, Carneiro Fatima, Berrino Franco, Sacerdote Carlotta, Tumino Rosario, Panico Salvatore, Berglund Göran, Simán Henrik, Stenling Roger, Hallmans Göran, Martínez Carmen, Bilbao Roberto, Barricarte Aurelio, Navarro Carmen, Quirós José R, Allen Naomi, Key Tim, Bingham Sheila, Khaw Kay-Tee, Linseisen Jakob, Nagel Gabriele, Overvad Kim, Tjonneland Anne, Olsen Anja, Bueno-de-Mesquita H Bas, Boshuizen Hendriek C, Peeters Petra H, Numans Mattijs E, Clavel-Chapelon Françoise, Boutron-Ruault Marie-Christine, Trichopoulou Antonia, Lund Eiliv, Offerhaus Johan, Jenab Mazda, Ferrari Pietro, Norat Teresa, Riboli Elio, González Carlos A
Unit of Epidemiology, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Av. Gran Via s/n km 2.7, 08907 Barcelona, Spain.
Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2427-34. doi: 10.1158/1055-9965.EPI-06-0072.
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.
代谢酶通常表现出基因多态性，参与烟草烟雾中存在的可能与胃癌发生相关的化合物的激活过程。我们报告了一项关于胃腺癌风险与CYP1A1、CYP1A2、EPHX1和GSTT1基因多态性之间关联的研究结果。在欧洲癌症与营养前瞻性调查（该调查在10个欧洲国家开展）中进行了一项巢式病例对照研究。该研究包括243例新诊断的经组织学确诊的胃腺癌病例和946例按中心、年龄、性别和采血日期匹配的对照。通过白细胞的核DNA确定基因型。我们发现，与携带TC/TT的受试者相比，EPHX1基因Y113H位点C（组氨酸）变体的纯合子患胃癌的风险增加（比值比，1.91；95%置信区间，1.19 - 3.07）。携带CYP1A1基因Ex7 + 129C>A（m4）至少一个变体等位基因A的吸烟者以及GSTT1基因缺失且CYP1A2基因 - 3859G>A位点为等位基因A的从不吸烟者患胃癌的风险也显著增加。这些基因大多参与多环芳烃的激活和解毒过程，表明这些化合物在胃癌发生中可能发挥作用。
