TY - JOUR
T1 - Impact of CYP3A4 and CYP3A5 single nucleotide polymorphisms on anastrozole-associated adverse events among Malaysian breast cancer patients
AU - Abubakar, Murtala B.
AU - Tan, Huay Lin
AU - Bhavaraju, Venkata Murali Krishna
AU - Gan, Siew Hua
N1 - Funding Information:
This work was supported by grant no. 1001/PPSP/853005 from Universiti Sains Malaysia (USM). The authors acknowledge the USM Global Fellowship [IPS/USMGF (01/14)] and Tertiary Education Trust Fund (TETFUND) awards to the first author.
Publisher Copyright:
© 2019, University of Malaya. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Adverse events
KW - Anastrozole
KW - Breast cancer
KW - CYP3A4
KW - CYP3A5
KW - PCR-RFLP
UR - http://www.scopus.com/inward/record.url?scp=85063537544&partnerID=8YFLogxK
U2 - 10.35118/apjmbb.2019.027.1.04
DO - 10.35118/apjmbb.2019.027.1.04
M3 - Article
AN - SCOPUS:85063537544
SN - 0128-7451
VL - 27
SP - 33
EP - 42
JO - Asia Pacific Journal of Molecular Biology and Biotechnology
JF - Asia Pacific Journal of Molecular Biology and Biotechnology
IS - 1
ER -