Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.
Keneuoe Cecilia NthonthoAndrew Khulekani NdlovuKirthana SharmaIshmael KasvosveDaniel Louis HertzGiacomo Maria PaganottiPublished in: Pharmacogenomics and personalized medicine (2022)
Breast cancer is the most frequent cause of cancer death in low- and middle-income countries, in particular among sub-Saharan African women, where response to available anticancer treatment therapy is often limited by the recurrent breast tumours and metastasis, ultimately resulting in decreased overall survival rate. This can also be attributed to African genomes that contain more variation than those from other parts of the world. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to specific available treatments and the known genetic variabilities associated with metabolism and/or transport of breast cancer drugs, and treatment outcomes when possible. The emphasis is on the African genetic variation and focuses on the genes with the highest strength of evidence, with a close look on CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, CYP19A1, UGT1A4, UGT2B7, UGT2B15, SLC22A16, SLC38A7, FcγR, DPYD, ABCB1 , and SULT1A1 , which are the genes known to play major roles in the metabolism and/or elimination of the respective anti-breast cancer drugs given to the patients. The genetic variability of their metabolism could be associated with different metabolic phenotypes that may cause reduced patients' adherence because of toxicity or sub-therapeutic doses. Finally, this knowledge enhances possible personalized treatment approaches, with the possibility of improving survival outcomes in patients with breast cancer.
Keyphrases
- end stage renal disease
- genome wide
- newly diagnosed
- ejection fraction
- chronic kidney disease
- stem cells
- healthcare
- squamous cell carcinoma
- dna methylation
- copy number
- adipose tissue
- mesenchymal stem cells
- patient reported outcomes
- combination therapy
- cell therapy
- young adults
- smoking cessation
- lymph node metastasis
- childhood cancer