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

• Main Authors: Kristina Bojanic, Lucija Kuna, Ines Bilic Curcic, Jasenka Wagner, Robert Smolic, Kristina Kralik, Tomislav Kizivat, Gordana Ivanac, Aleksandar Vcev, George Y. Wu, Martina Smolic
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: single nucleotide polymorphism; drug metabolizing enzyme; breast cancer therapy; anastrozole; side effects
• Online Access: https://www.mdpi.com/1660-4601/17/10/3692
• ISSN: 1661-7827; 1660-4601

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.