Impact of CYP3A4 and CYP3A5 single nucleotide polymorphisms on anastrozole-associated adverse events among Malaysian breast cancer patients

Murtala B. Abubakar, Huay Lin Tan, Venkata Murali Krishna Bhavaraju, Siew Hua Gan

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    The catalytic activity of the cytochrome P450A (CYP3A4) enzyme is reportedly affected by the presence of single nucleotide polymorphisms (SNPs), leading to inter-individual variability in drug efficacy and adverse reactions. CYP3A4 polymorphisms can serve as potential biomarkers for predicting the efficacy of many drugs, including those used in breast cancer treatment. This study was conducted on 94 hormone receptor-positive postmenopausal breast cancer patients who received 1 mg of anastrozole per day. Anastrozole-associated adverse events (AAAEs), such as musculoskeletal adverse events (MSAEs), hot flashes, mood disturbance and vaginal dryness/dyspareunia, were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to determine the allelic frequency of CYP3A4*4, CYP3A4*18A, CYP3A4*18B, CYP3A4*22 and CYP3A5*3. The frequencies of CYP3A4*18A T>C (rs28371759), CYP3A4*18B G>A (rs2242480) and CYP3A5*3 were 0.03, 0.48 and 0.64, respectively. However, no CYP3A4*4 A>G (rs55951658) or CYP3A4*22 C>T (rs35599367) alleles were detected. No significant association was observed between the alleles and the development of AAAEs. We have demonstrated for the first time that CYP3A4*18B G>A is highly prevalent among Malaysian breast cancer patients. The clinical relevance of CYP3A4*18B is currently under investigation by our group.

    Original languageEnglish
    Pages (from-to)33-42
    Number of pages10
    JournalAsia-Pacific Journal of Molecular Biology and Biotechnology
    Volume27
    Issue number1
    DOIs
    Publication statusPublished - 2019

    Keywords

    • Adverse events
    • Anastrozole
    • Breast cancer
    • CYP3A4
    • CYP3A5
    • PCR-RFLP

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