Variable Number of Tandem Repeats (VNTR) gene polymorphism of CYP2E1 in patients with pancreatic adenocarcinoma

Abstract

Context: The genetic polymorphism is considered a major source of variability, influencing the levels of gene expression. Cytochrome P450 2E1 (CYP2E1) is a mixed-function oxidase involved in the metabolism of the many endogenous and exogenous substances (ethanol, chemical carcinogens) in the hepatic and pancreatic tissue. CYP2E1 gene polymorphisms can cause various abilities of metabolize xenobiotic substances within a population with consequent increased susceptibility to various diseases,including cancer. One of the polymorphisms of the CYP2E1 gene is a VNTR (Variable Number Tandem Repeat) of some sequences in its "5 '- flanking region. Method : VNTR genotype CYP2E1 was determined by RFLP-PCR performed on DNA extracted from peripheral blood lymphocytes and paraffin embedded tissue of central-western Sicilia population with PA, to confirm or exclude a correlation between certain genotypes and specific disease. A population of university students, without specific overt disease, was used as control . Results: The modal genotype, found in all subjects, was CYP2E1 VNTR A2/A2, while CYP2E1 VNTR A2/A4 was the least represented in both populations. The A2/A3 genotype was different between patients with pancreatic cancer and healthy subjects, suggesting a correlation between this genotype and pancreatic cancer. Recent studies indicated A2 allele might be associated with a negative regulation of the gene and nothing about it has been reported for the allele A3. Conclusion: Our preliminary data indicate an association between genotype A2/A3 and PA and allow us to hypothesize that the A3 allele is associated with low activity of the CYP2E1 gene. Consequently, individuals with this allelic association may have inadequate ability to metabolize toxic xenobiotic substances, condition that might increase the susceptibility to develop some cancer, including PA.