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Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma
Author(s) -
Tsukino Hiromasa,
Kuroda Yoshiki,
Qiu Delai,
Nakao Hiroyuki,
Imai Hirohisa,
Katoh Takahiko
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10492
Subject(s) - cyp2e1 , genotype , cytochrome p450 , gastric adenocarcinoma , cyp2d6 , gene , medicine , genetics , biology , adenocarcinoma , cyp3a , microbiology and biotechnology , cancer , pharmacology , chemistry , metabolism
Cytochrome P450 (CYP) 2A6 and CYP2E1 are enzymes with a high ability to activate a nitrosamine, 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), to its potent and ultimate carcinogens. The polymorphic CYP2A6 and CYP2E1 have been implicated in increased susceptibility to certain malignancies. In our study, 120 Japanese patients with gastric adenocarcinoma and 158 healthy controls were compared for frequencies of CYP2A6 and CYP2E1 genotypes. The frequency with which the subjects carried homozygotes of the CYP2A6 gene deletion allele, which causes lack of the enzyme activity, was significantly higher in the gastric cancer patients than in the healthy control subjects (OR = 3.14, 95% confidence interval (95% CI) = 1.05–9.41). Subdividing gastric adenocarcinoma according to tumor differentiation, patients with the well‐differentiated type were 4.9‐fold more likely to have the CYP2A6 homozygote deletion genotype (OR = 4.91, 95% CI 1.17–20.52). Stratifying by smoking status, we did not find the risk of CYP2A6 gene deletion allele in gastric adenocarcinoma. The CYP2E1 polymorphism detected by Rsa I was not significantly different between gastric adenocarcinoma patients (40.8%) and the control population (44.3%). No statistically significant changes were observed when the CYP2E1 genotype was examined relative to tumor differentiation and smoking status. These results suggest that the CTY2A6 deletion is associated with gastric adenocarcinoma among Japanese populations. © 2002 Wiley‐Liss, Inc.