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Open AccessArticle

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

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Department of Biophysics and Radiology, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Department of Biophysics and Radiology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Department of Radiology, Health Center Osijek, 31000 Osijek, Croatia
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Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Department of Medicine, Division of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia
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Department of Medical Biology and Genetics, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Department of Pathophysiology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Department of Medicine, Division of Gastroenterology/Hepatology, University Hospital Osijek, 31000 Osijek, Croatia
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Department of Medical Statistics and Medical Informatics, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Clinical Institute for Nuclear Medicine and Radiation Protection, University Hospital Osijek, 31000 Osijek, Croatia
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Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Department of Diagnostic and Interventional Radiology, University Hospital Dubrava, 10000 Zagreb, Croatia
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University of Zagreb School of Medicine, Salata 3, 10000 Zagreb, Croatia
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Department of Medicine, Division of Gastrenterology/Hepatology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06032, USA
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Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2020, 17(10), 3692; https://doi.org/10.3390/ijerph17103692
Received: 30 April 2020 / Revised: 21 May 2020 / Accepted: 21 May 2020 / Published: 23 May 2020
(This article belongs to the Special Issue Breast Cancer Genetics)
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. View Full-Text
Keywords: single nucleotide polymorphism; drug metabolizing enzyme; breast cancer therapy; anastrozole; side effects single nucleotide polymorphism; drug metabolizing enzyme; breast cancer therapy; anastrozole; side effects
MDPI and ACS Style

Bojanic, K.; Kuna, L.; Bilic Curcic, I.; Wagner, J.; Smolic, R.; Kralik, K.; Kizivat, T.; Ivanac, G.; Vcev, A.; Wu, G.Y.; Smolic, M. Representation of CYP3A4, CYP3A5 and UGT1A4 Polymorphisms within Croatian Breast Cancer Patients’ Population. Int. J. Environ. Res. Public Health 2020, 17, 3692.

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