| Popis: |
The genetic polymorphism of the enzymes involved in the metabolism of drugs and environmental carcinogens has an important role in adverse therapeutic effects or prevalence of cancer. CYP2D6, the isoform of the cytochrome P-450 metabolizing more than 25 percent of most common drugs, has more than 17 different allelic variants identified to date. The mutant CYP2D6 A allele with A deletion in exon V and mutant CYP2D6 B allele with G1934A, splice site defect, are among the most common. These mutations result in no activity of CYP2D6 isoenzyme and contribute to poor metabolizer phenotype. As in many other cancer forms CYP2D6 enzyme in the breast cancer may have an important role in regulating the capacity of individual breast cells to metabolize hormones and environmental carcinogens. Very little is known about the relationship between CYP2D6 mutants (poor metabolizers) and susceptibility to breast cancer. The aim of this study was to investigate CYP2D6 A and B mutant frequencies in breast cancer patients. Genotyping of the CYP2D6 A and B alleles was performed on whole blood DNA of patient (n=44) and control (healthy volunteers, n=33) group by PCR-RFLP method. Upon exon IV (B allele) and exon V (A allele) amplification, the PCR products thus obtained (355 bp and 270 bp, respectively) were cleaved by Mva I and Msp I restriction endonucleases, and genotype of each sample was determined by electrophoresis of the cleavage products on 3 percent agarose gel. Study results showed that out of 33 controls studied for B allele, 23 (70 percent) were wild type and 10 (30 percent) were detected to bear B allele: 9 (27 percent) of them were found to be heterozygous and 1 (3 percent) homozygous. Among 33 controls there was no A allele. Among 44 patients, no one had A allele, 25 (57 percent) were genotyped as wild type and there were 19 (43 percent) patients with B allele: 16 (36 percent) of them heterozygous, 3 (7 percent) homozygous. Statistical analysis (Chi square test) showed that frequencies of CYP2D6 A and B mutant alleles did not differ significantly between control and patient group (P=0.472) These preliminary results indicate that further study should be done to confirm our findings and the patient group should be expanded. |
