engleski

PHARMACOGENETICS OF ANASTRAZOLE DRUG- METABOLIZING ENZYMES AND THEIR IMPACT ON BONE MINERAL DENSITY IN CROATIAN BREAST CANCER WOMEN

Background: Cancer poses a major public health problem worlwide. Breast cancer (BC) is the second most common cancer diagnosed in women in Croatia. Anastrozole has demonstrated a longer disease-free survival and better overall safety in the adjuvant treatment of BC. Single nucleotide polymorphism (SNP) in genes encoding drug metabolizing enzymes could have key role in the individual response to anastrozole therapy and drug safety. Objective: To investigate rates of CYP3A4*1B, CYP3A5*3 and UGT1A4*2 SNPs significant in anastrozole metabolism in BC women in Croatia and its potential correlation to anastrozole induced side effects. Methods: 82 postmenopausal women with estrogen receptor (ER)-positive BC treated with anastrozole and 44 BC controls before therapy were included in the study. DNA for SNPs was genotyped by TaqMan RT-PCR and bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). Results: Mutant G allele homozygotes were predominant 88%, and homozygotes for the wild type A allele of CYP3A5*3 were not found. Furthermore 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 anastrozole and without treatment, respectively. Total hip and femoral neck BMD were lower in the group treated with anastrozole. However, potential correlation of BMD changes induced by anastrozole therapy with prevalence of explored SNPs was not shown. Conclusion: No significant differences in BMD among the groups were confirmed. Although, the mutant CYP3A5*3 SNP was predominant and may result in low anastrozole metabolism.

breast cancer, anastrazole, single nucleotide polymorphism

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