GENOTYPING OF THE CYP1A1 AND GSTM1 GENES IN ESOPHAGEAL-CARCINOMA PATIENTS WITH SPECIAL REFERENCE TO SMOKING

BACKGROUND. Aromatic hydrocarbons, including benzol[a]pyrene, in tobac co smoke first require metabolic activation by phase I enzymes, cytoch rome P450s (CYP450s), and then are subjected to detoxification by phas e II enzymes, the glutathione-S-transferases. A high risk lung carcino ma group has been reported to have specific polymorphisms of the cytoc hrome P450 (CYP1A1) gene and the glutathione-S-transferase (GSTM1) gen e. In this study, the authors investigated whether such genotypes were also risk factors for esophageal carcinoma. METHODS. Subjects were co mprised of 89 esophageal carcinoma patients and 137 noncancer controls . Forty-nine of the patients and 60 of the control subjects were smoke rs. Genotypic studies of both CYP1A1 and GSTM1 were performed in the c ancer tissues of all 89 patients. Genotypes of peripheral blood leukoc ytes taken from the control subjects were also determined. Genotypes o f the CYP1A1 and GSTM1 genes were determined by the polymerase chain r eaction. RESULTS. Patients who were heavy smokers with the genotypes V al/Val (V/V) for CYP1A1 and the combined genotype of V/V for CYP1A1 an d 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 CYP1A1 with a smoking index greater than or equal to 600 in esophageal carcinoma patients was estimated at 6.63 (95% confidence interval [CI], 1.86-23.7). The association of combine d genotypes of V/V of CYP1A1 and GSTM1 with a smoking index greater th an or equal to 600 in esophageal carcinoma patients was estimated at 1 2.7 (95% CI, 1.97-81.8). CONCLUSIONS. Specific genotypes of the CYP1A1 and GSTM1(-) genes are related to the incidence of esophageal carcino ma, especially in heavy smokers. (C) 1997 American Cancer Society.