Genotyping of the CYP1A1 and GSTM1 genes in esophageal carcinoma patients with special reference to smoking.
BACKGROUND
Aromatic hydrocarbons, including benzol[a]pyrene, in tobacco smoke first require metabolic activation by phase I enzymes, cytochrome P450s (CYP450s), and then are subjected to detoxification by phase II enzymes, the glutathione-S-transferases. A high risk lung carcinoma group has been reported to have specific polymorphisms of the cytochrome P450 (CYP1A1) gene and the glutathione-S-transferase (GSTM1) gene. In this study, the authors investigated whether such genotypes were also risk factors for esophageal carcinoma.


METHODS
Subjects were comprised of 89 esophageal carcinoma patients and 137 noncancer controls. Forty-nine of the patients and 60 of the control subjects were smokers. Genotypic studies of both CYP1A1 and GSTM1 were performed in the cancer tissues of all 89 patients. Genotypes of peripheral blood leukocytes taken from the control subjects were also determined. Genotypes of the CYP1A1 and GSTM1 genes were determined by the polymerase chain reaction.


RESULTS
Patients who were heavy smokers with the genotypes Val/Val (V/V) for CYPIAI and the combined genotype of V/V for CYP1A1 and GSTM1- were a statistically high risk group compared with control subjects (P < 0.01, chi-square = 10.6 vs. P < 0.01, chi-square = 11.0). The association of V/V for CYPIAI with a smoking index > or = 600 in esophageal carcinoma patients was estimated at 6.63 (95% confidence interval [CI], 1.86-23.7). The association of combined genotypes of V/V of CYP1A1 and GSTM1 with a smoking index > or = 600 in esophageal carcinoma patients was estimated at 12.7 (95% CI, 1.97-81.8)


CONCLUSIONS
Specific genotypes of the CYP1A1 and GSTM1- genes are related to the incidence of esophageal carcinoma, especially in heavy smokers.
Nimura
Y
Y
Department of Surgery, Shinshu University, School of Medicine, Asahi, Matsumoto, Japan.
Yokoyama
S
S
Fujimori
M
M
Aoki
T
T
Adachi
W
W
Nasu
T
T
He
M
M
Ping
Y M
YM
Iida
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001564:Benzo(a)pyrene / Q000378:metabolism; D001711:Biotransformation; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic; D007527:Isoenzymes / Q000235:genetics; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D014633:Valine / Q000235:genetics
D007527:Isoenzymes; D007532:Isoleucine; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D014633:Valine