Association between genetic polymorphisms of the cytochromes P-450 (1A1, 2D6, and 2E1) and the susceptibility to pancreatic cancer.

Abstract

OBJECTIVES: Metabolic activation is a prerequisite for the carcinogenic effect of many carcinogens, and considerable interindividual variation exists in the metabolic capacity to activate the carcinogens. The cytochromes P-450 (CYPs) are responsible for the activation mechanism, and polymorphisms of the CYPs (CYP1A1, CYP2D6, and possibly CYP2E1) are known to be related to increased susceptibility to smoking related Kreyberg type I lung cancer. The aim of this study is to clarify the relationship of genetic polymorphisms of the CYPs to susceptibility to pancreatic cancer, another smoking-related cancer. METHODS: We analyzed 45 samples from patients with pancreatic cancer and 53 samples from controls. DNA was isolated from blood samples and the CYP1A1, 2D6 and 2E1 genes were amplified by PCR. Analyzing the genotypes of the CYPs by allele-specific PCR or RFLP analysis, we assessed the allele frequencies for each mutation of the CYPs among the patients with pancreatic cancer and the controls. RESULTS: The allele frequencies for the mutation in the 3'-flanking region of the CYP1A1 among the cases and the controls were 0.31 and 0.36, respectively. The allele frequencies for the exon 7 mutation of the CYP1A1 were 0.16 and 0.23, respectively, but with no statistical significance. The frequencies for the mutant c2 allele of the CYP2E1 were 0.19 and 0.30, respectively, but with no statistical significance. Two persons homozygous for a gene deletion of the CYP2D6 were observed among control subjects; other mutations were not observed among either the patients or controls. CONCLUSION: We could not find any evidence that polymorphisms of the CYPs are associated with increased susceptibility to pancreatic cancer.