Representation of CYP3A4, CYP3A5 and UGT1A4 Polymorphisms within Croatian Breast Cancer Patients’ Population

International Journal of Environmental Research and Public Health

Tomislav Kizivat¹  Kristina Bojanic²  Gordana Ivanac³  Jasenka Wagner⁴  Kristina Kralik⁵  George Y. Wu⁶  Aleksandar Vcev⁷  Robert Smolic⁷  Martina Smolic⁸  Lucija Kuna⁸  InesBilic Curcic⁹ 

[1] Clinical Institute for Nuclear Medicine and Radiation Protection, University Hospital Osijek, Osijek 31000, Croatia;Department of Biophysics and Radiology, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia;Department of Diagnostic and Interventional Radiology, University Hospital Dubrava, Zagreb 10000, Croatia;Department of Medical Biology and Genetics, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia;Department of Medical Statistics and Medical Informatics, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia;Department of Medicine, Division of Gastrenterology/Hepatology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06032, USA;Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia;Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia;Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia;

关键词: single nucleotide polymorphism;    drug metabolizing enzyme;    breast cancer therapy;    anastrozole;    side effects;   

DOI  :  10.3390/ijerph17103692

来源: DOAJ

【 摘 要 】

Single nucleotide polymorphism (SNP) in genes encoding drug-metabolizing enzymes (DME) could have a critical role in individual responses to anastrozole. Frequency of CYP3A4*1B, CYP3A5*3 and UGT1A4*2 SNPs in 126 Croatian breast cancer (BC) patients and possible association with anastrozole-induced undesirable side effects were analyzed. Eighty-two postmenopausal patients with estrogen receptor (ER)-positive BC treated with anastrozole and 44 postmenopausal ER-positive BC patients before hormonal adjuvant therapy were included in the study. Genomic DNA was genotyped by TaqMan Real-Time PCR. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The homozygotes for the variant G allele of CYP3A5*3 were predominant (88%), and the homozygotes for the reference A allele were not detected. While homozygotes for the variant G allele of CYP3A4*1B were not detected, predominantly wild type homozygotes for A allele (94%) were present. CYP3A4*1B and CYP3A5*3 SNPs were in 84.3% linkage disequilibrium (D’ = 0.843) and 95.1% (D’ = 0.951) in group treated with anastrozole and w/o treatment, respectively. Homozygotes for the A allele of UGT1A4*2 were not detected in our study groups. Although the variant CYP3A5*3 allele, which might result in poor metabolizer phenotype and more pronounced side effects, was predominant, significant association with BMD changes induced by anastrozole were not confirmed.

【 授权许可】

Unknown