Association of single nucleotide polymorphisms of cytochrome P450 enzymes with experience of vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients: a systematic review

Abstract Background Adjuvant endocrine therapies are known to induce undesirable adverse effects such as vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients. Drugs used in these therapies are often metabolised by cytochrome P450 (CYP) enzymes, in which their metabolising activities can be modified by single nucleotide polymorphisms (SNP) in CYP genes and CYP genotypes. This review aims to explore whether SNPs or genotypes of CYP are associated with the occurrence, frequency and severity of vasomotor, vaginal and musculoskeletal symptoms in breast cancer patients on adjuvant endocrine therapies. Methods A literature review was conducted using five electronic databases, resulting in the inclusion of 14 eligible studies, and their findings were presented narratively. Selected items from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist were used for critical appraisal of the reporting quality of the included studies. Results Most of the included studies showed that SNPs or genotypes of CYP that modify its metabolising activity have no effect on the occurrence, frequency or severity of vasomotor symptoms, including hot flashes. One study showed no correlation of these genetic variations in CYP with musculoskeletal symptoms, and no data were available on the association between such genetic variations and vaginal symptoms. Conclusions Overall, genetic variations in CYP have no effect on the experience of hot flashes among breast cancer patients. We recommend exploration of the link between the active metabolites of chemotherapeutic drugs and the molecules shown to affect the occurrence or severity of hot flashes, and the establishment of the relationship between such genetic variations and patients’ experience of musculoskeletal and vaginal symptoms. Subgroup analyses based on patients’ duration of adjuvant endocrine therapies in such studies are recommended.

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

Asia Pacific Journal of Molecular Biology and Biotechnology ◽

10.35118/apjmbb.2019.027.1.04 ◽

2019 ◽

pp. 33-42

Author(s):

Murtala B. Abubakar ◽

Huay Lin Tan ◽

Venkata Murali Krishna Bhavaraju ◽

Siew Hua Gan

Keyword(s):

Breast Cancer ◽

Single Nucleotide Polymorphisms ◽

Adverse Events ◽

Cancer Patients ◽

Hot Flashes ◽

Postmenopausal Breast Cancer ◽

Individual Variability ◽

Nucleotide Polymorphisms ◽

Breast Cancer Patients ◽

Single Nucleotide

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.

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