Pharmacogenomics and Personalized Medicine (Jun 2022)
Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective
Abstract
Keneuoe Cecilia Nthontho,1,2 Andrew Khulekani Ndlovu,1 Kirthana Sharma,3 Ishmael Kasvosve,1 Daniel Louis Hertz,4 Giacomo Maria Paganotti2,5,6 1School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana; 2Botswana-University of Pennsylvania Partnership, Gaborone, Botswana; 3Rutgers Global Health Institute, New Brunswick, NJ, USA; 4Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA; 5Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6Department of Biomedical Sciences, Faculty of Medicine, University of Botswana, Gaborone, BotswanaCorrespondence: Giacomo Maria Paganotti, Botswana-University of Pennsylvania Partnership, PO Box 45498, Riverwalk Gaborone, Botswana, Tel +267 3555375, Email [email protected]: 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.Keywords: breast cancer, genetic variability, inter-ethnic differences, pharmacogenetics, sub-Saharan Africa, toxicity
