{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:58:34Z","timestamp":1775278714477,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","award":["EMU grant"],"award-info":[{"award-number":["EMU grant"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Tamoxifen is widely used in the treatment of hormone receptor-positive breast cancer and has been shown to successfully reduce recurrence and mortality rates. Nonetheless, variability in patient response to tamoxifen treatment is observed with up to 40% of patients experiencing recurrence. Genetic polymorphisms in pharmacogenes encoding enzymes involved in tamoxifen metabolism have been linked to some of this observed interindividual variability. The pharmacogenetics of tamoxifen in populations of African descent remain understudied, creating difficulties in pinpointing the primary factors behind the observed variable response. To address this gap, this study aimed to investigate the role of genetic variation in tamoxifen treatment outcomes in a South African cohort. Methods: Participants included 166 Mixed and African Ancestry breast cancer patients who had received tamoxifen treatment. Genetic characterization was performed for 53 single nucleotide polymorphisms (SNPs) and two copy number variations across eight drug-metabolizing enzymes, including cytochrome P450s (CYP2D6, CYP3A4, CYP3A5, CYP2B6), UDP-glucuronosyltransferases (UGT1A4), and sulfotransferases (SULT1A1, SULT1E1, SULT2A1). The association between genotypes and disease-free survival (DFS) was evaluated using Cox proportional hazards regression models. Results: The CYP2B6*1\/*6 or *4\/*9 genotype showed a nominal association with improved DFS (p = 0.049), with a similar trend observed for UGT1A4 rs11888492. In contrast, SULT1E1 rs3775779 heterozygosity showed a nominal association with reduced DFS (p = 0.044). SULT1A1 SNPs (rs4149393, rs4149394, rs1042157) demonstrated trends toward reduced DFS. Conclusions: These exploratory findings highlight the need for more inclusive pharmacogenomic research and point to potential biomarkers for optimizing tamoxifen therapy in African populations.<\/jats:p>","DOI":"10.3390\/jpm16040188","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variation in CYP2B6, UGT1A4 and Sulfotransferases Is Associated with Disease-Free Survival in South African Breast Cancer Patients Treated with Tamoxifen"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1027-6660","authenticated-orcid":false,"given":"Bianca","family":"Kruger","sequence":"first","affiliation":[{"name":"Platform for Pharmacogenomics Research and Translation (PREMED), South African Medical Research Council, Cape Town 7700, South Africa"},{"name":"Pharmacogenomics and Drug Metabolism Research Group, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-2047","authenticated-orcid":false,"given":"Emile R.","family":"Chimusa","sequence":"additional","affiliation":[{"name":"Bioinformatic and Multi-Omics Data Science Group, Faculty of Science and Environment, Northumbria University, Newcastle NE1 8ST, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aron B.","family":"Abera","sequence":"additional","affiliation":[{"name":"Inqaba Biotechnical Industries, Pretoria 0002, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3502-9546","authenticated-orcid":false,"given":"Jesmika","family":"Singh","sequence":"additional","affiliation":[{"name":"Platform for Pharmacogenomics Research and Translation (PREMED), South African Medical Research Council, Cape Town 7700, South Africa"},{"name":"Pharmacogenomics and Drug Metabolism Research Group, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2355-6629","authenticated-orcid":false,"given":"Delva","family":"Shamley","sequence":"additional","affiliation":[{"name":"Division of Clinical Anatomy and Biological Anthropology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-4895","authenticated-orcid":false,"given":"Collet","family":"Dandara","sequence":"additional","affiliation":[{"name":"Platform for Pharmacogenomics Research and Translation (PREMED), South African Medical Research Council, Cape Town 7700, South Africa"},{"name":"Pharmacogenomics and Drug Metabolism Research Group, Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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