title: A polymorphism in the 5'-flanking region of the CYP2E1 gene and elevated lung adenocarcinoma risk in a Japanese population.
abstract: Cytochrome P450 2E1 (CYP2E1) catalyzes the metabolic activation of the procarcinogen, N-nitrosodimethylamine, and cytotoxic carbon tetrachloride compounds. A tandem repeat polymorphism in the 5'-flanking region of the CYP2E1 gene was investigated in non-small cell lung carcinoma (NSCLC) patients to clarify the relationship between CYP2E1 gene polymorphism and lung cancer susceptibility. Blood samples were taken from 236 healthy control subjects (192 males and 44 females) and 111 patients (78 males and 33 females) who underwent surgery for NSCLC in Japan. DNA was isolated from these samples and the 5'-flanking region of the CYP2E1 gene was amplified by polymerase chain reaction and examined for tandem repeat polymorphisms using DNA fragment analysis. Sequence analysis confirmed the presence of three alleles, A2, A3, and A4 (361, 367, and 457 bp, respectively), with four genotypes observed in the lung cancer group and five genotypes in the control group. There was a statistically significant difference in genotype distribution between the lung adenocarcinoma and control group (P=0.0088, A4/A4 vs. non-A4/A4). In the lung adenocarcinoma group, the univariate risk estimates for the A4/A4 subgroup compared to the most common subgroup (A2/A2) was 4.300 (95% confidence interval = 1.358-13.618, P=0.0131). We conclude that the A4/A4 genotype of the 5'-flanking region of CYP2E1 was significantly more frequent in lung adenocarcinoma cases than in healthy controls and, therefore, may be involved in the development of lung adenocarcinoma.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iizasa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Baba
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Haga
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Hao
authors.initials: H
authors.lastname: Chang
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.forename: Sakae
authors.initials: S
authors.lastname: Itoga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D001483:Base Sequence; D002273:Carcinogens; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004128:Dimethylnitrosamine; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009602:Nitrosamines; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid; D012306:Risk; D017422:Sequence Analysis, DNA
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; D004247:DNA; D019392:Cytochrome P-450 CYP2E1; D004128:Dimethylnitrosamine