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

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.