Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma.
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 RsaI 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.
Department of Public Health, School of Medicine, Miyazaki Medical College, Miyazaki, Japan.
Hiromasa
H
Tsukino
Yoshiki
Y
Kuroda
Delai
D
Qiu
Hiroyuki
H
Nakao
Hirohisa
H
Imai
Takahiko
T
Katoh
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6