engleski

RATES OF CYP3A4, CYP3A5 AND UGT1A4 SINGLE NUCLEOTIDE POLYMORFISMS IN CROATIAN BREST CANCER PATIENTS AND ITS LINKAGE TO ANASTROZOLE INDUCED CHANGES OF BONE MINERAL DENSITY

Introduction: Breast cancer (BC) is the most common malignant disease in females taking 26 % of all cancer sites. Third generation aromatase inhibitors like anastrozole are becoming more important in treating BC because of their efficacy and better overall safety in the adjuvant treatment. Single nucleotide polymorphism (SNP) in genes encoding drug metabolizing enzymes could have an important role in individual responses to anastrozole therapy including drug efficacy and side effects. Aim: To explore rates of three SNPs (CYP3A4*1B, CYP3A5*3, UGT1A4*2) important in anastrozole metabolism in population of Croatian BC patients, and its possible correlation to anastrozole induced side effects. Materials and methods: 126 BC patients were included in the study of which 82 were postmenopausal patients with ER positive BC treated with anastrozole and 44 were postmenopausal ER positive patients before hormonal adjuvant therapy. DNA for SNPs was genotyped by TaqMan RT-PCR and BMD was measured by DXA. Results: Homozygotes for the wild type A allele of CYP3A5*3 were not detected, moreover mutant G allele homozygotes were predominant with 88%. Wild type homozygotes of CYP3A4*1B were predominant with 94%, and mutant homozygotes were not detected. CYP3A4*1B and CYP3A5*3 SNPs were in 84.3% linkage disequilibrium and 95.1% in group treated with anastrozol and without treatment. Possible association of BMD changes induced by anastrozole therapy with prevalence of the three explored SNPs was not demonstrated. Conclusion: Even though the mutant CYP3A5*3 SNP was predominant, which may result in poor anastrozole metabolism, no significant differences in BMD between the groups were confirmed.

anastrozole ; polymorphism, single nucleotide ; bone density

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