{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:25:26Z","timestamp":1782854726863,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001332","name":"Council for Scientific and Industrial Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001332","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Cape Town Research Council"},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Academy of Medical Sciences Professorship","award":["#APR9\\1024"],"award-info":[{"award-number":["#APR9\\1024"]}]},{"name":"National Research Foundation-Ministry of Higher Education and Scientific Research (NRF-MHESR) Bilateral Project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Tamoxifen remains the cornerstone of endocrine therapy for hormone receptor-positive breast cancer across Africa. Understanding the factors that influence tamoxifen tolerability is critical, as treatment-related side effects can reduce adherence and compromise therapeutic outcomes. Yet, the contribution of pharmacogenetic variation to tamoxifen-related toxicity remains poorly characterized in African populations. This study, therefore, investigated whether genetic variation in key pharmacogenes influences the risk of treatment-related side effects in a South African breast cancer cohort. Methods: A total of 166 women of Mixed and African Ancestry treated with 20 mg\/day tamoxifen at Groote Schuur Hospital, South Africa, were included in the study. Genetic variation across 28 variants in nine pharmacogenes, including CYP2D6, CYP3A4\/5, UGT1A4, UGT2B7\/15, SULT1A1\/2, and SULT1E1, was assessed using various genotyping methods. Associations between genetic and non-genetic factors and tamoxifen side effects were evaluated with logistic regression. Results: Over 70% of participants reported at least one treatment-related side effect. Overall side-effect burden was associated with SULT1A1 copy number variation (p = 0.030) and SULT1E1 rs3736599 (p = 0.042). Musculoskeletal complaints were the most common (40%) and were associated with UGT2B7 rs7439366 (p = 0.040) and CYP3A4 rs2242480 (p = 0.051). Gynecological symptoms affected more than 20% of participants and were linked to SULT1A2*2 (p = 0.050), SULT1E1 rs3736599 (p = 0.016), and UGT2B15 rs4148269 (p = 0.039). Hot flashes were frequent, affecting 33% of patients, but showed no clear pharmacogenetic associations. Conclusions: This study demonstrates that pharmacogenetic variation is associated with interindividual differences in treatment-related side effects, underscoring the need to expand research in African populations to better inform precision endocrine therapy.<\/jats:p>","DOI":"10.3390\/genes17030252","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:19:23Z","timestamp":1771935563000},"page":"252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SULT and UGT Genetic Variants Modulate Side Effect Profiles in South African Breast Cancer Patients Treated with Tamoxifen"],"prefix":"10.3390","volume":"17","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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-2047","authenticated-orcid":false,"given":"Emile","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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aron","family":"Abera","sequence":"additional","affiliation":[{"name":"Inqaba Biotechnical Industries, Pretoria 0002, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"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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