CYP2D6 genotyping of breast cancer patients under treatment with tamoxifen in Gaza Strip

Abstract

Introduction: Tamoxifen is the standard antihormonal therapy for breast cancer. It undergoes chemical digestion to more active compounds inside the liver microsome through the cytochrome P450 isoform CYP2D6, an enzyme encoded on CYP2D6 gene. CYP2D6 is polymorphic in which polymorphisms alter the enzyme activity by means of poor metabolism, intermediate metabolism, and ultra-rapid metabolism. Objectives: the study aimed to genotype palestinian breast cancer patients for common polymorphisms that lower or abolish CYP2D6 activity (CYP2D6*3, *4, *6, *9, *10, and *17), as well studying the effect of polymorphisms on the clinical outcome and establishing the role of pharmacogenetics in disease follow up. Methodology: Fifty eight whole blood samples were submitted to DNA extraction with affenity column technology, followed by long range PCR and a newly designed allele-specific PCR. Data were collected from medical records; in addition, patients were interviewed. All data were analyzed by SPSS software version 21. Results: two patients had the genotype *1/*3, three patients had the genotype *1/*4, one patient with the genotype *9/*9, one patient with the genotype *3/*10, and negative results for *17 allele. The allelic frequencies for *3, *4, *9, and *10 alleles were 2.59%, 2.59%, 4.3%, and 0.86%, respectively. The study showed a significant correlation between the appearance of alleles and the clinical outcomes. Conclusion: there was a significant allele frequency among the study population, and the presence of allelic variants led to a noteworthy effect on the clinical outcome of tamoxifen therapy; therefore, tamoxifen pharmacogenetic assessment plays a key role in treatment success. Key words: Breast cancer, Genotyping, CYP2D6, Polymorphism, Pharmacogenetics, Gaza strip.