Human CYP2D6 gene polymorphism in Slovene cancer patients and healthy controls.

ABSTRACT

The polymorphic CYP2D6 gene encoding debrisoquine hydroxylase has attracted much interest for its possible role in human pulmonary carcinogenesis. The purpose of this work was to determine the frequency of poor metabolizers (PM) and extensive metabolizers (EM) of debrisoquine in Slovene population of healthy individuals (n = 107), lung cancer patients (200) and melanoma patients (121). Polymorphism of CYP2D6 gene was studied by genotyping based on PCR analysis of the intron 3 exon 4 junction containing G to A mutation and one base pair deletion in exon 5, which are responsible for approximately 95% of poor metabolizer phenotype in Caucasians. In the healthy Slovene population 62.5% of individuals were identified as extensive metabolizers, 31% as extensive-heterozygous metabolizers and 6.5% as poor metabolizers of debrisoquine. The frequency of EM individuals was 70.5% in lung cancer patients and 64% in melanoma patients, the frequency of extensive-heterozygous subjects was 27% in lung cancer patients and 31% in melanoma patients. The frequency of PM individuals in the lung cancer patients was 2.5% and in melanoma patients 5%. The decrease in PM genotype in the group of Slovene lung cancer patients is similar to the decrease published for some other ethnic groups. Our results support the hypothesis that polymorphic CYP2D6 gene probably plays some, though not a prevalent role in chemical carcinogenesis. Poor metabolizer individuals appear to be less susceptible to lung cancer than EM individuals.