{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:52:28Z","timestamp":1785430348167,"version":"3.56.0"},"reference-count":63,"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":"crossref","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05q60vz69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["23030881391"],"award-info":[{"award-number":["23030881391"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Breast cancer susceptibility gene 1 (BRCA1) is a pivotal regulator of DNA repair, and its loss through germline mutations is strongly linked to the development of aggressive breast cancers with characteristic clinical and pathological features. Beyond genetic disruption, epigenetic silencing via promoter hypermethylation has emerged as a non-mutational mechanism of tumour suppressor inactivation and a potential biomarker for guiding therapeutic decisions. Here, we investigate BRCA1 promoter methylation, its impact on gene expression, and its association with clinicopathological features in a cohort of African women with breast cancer. Methods: Matched tumour and adjacent normal tissues from 27 Black African women with breast cancer were analysed for BRCA1 promoter methylation and gene expression using bisulfite pyrosequencing and quantitative real-time PCR. Associations with clinicopathological variables were assessed using Spearman\u2019s correlation analyses. Results: Five CpG sites within the BRCA1 promoter were significantly hypermethylated in breast tumours compared with matched adjacent normal tissues and showed an inverse association with BRCA1 mRNA expression. Elevated promoter methylation was enriched in hormone receptor-negative and triple-negative breast cancer subtypes and was not influenced by neoadjuvant chemotherapy. BRCA1 promoter methylation occurred independently of BRCA1 mutational status. No significant associations were observed between BRCA1 methylation and age, body mass index, smoking status, or alcohol consumption. Conclusions: Our findings provide evidence of BRCA1 epigenetic silencing in breast tumours from African women, particularly within aggressive hormone receptor-negative subtypes. These results suggest that BRCA1 promoter methylation may represent a clinically informative biomarker for patient stratification and highlight the importance of validation in larger, population-representative cohorts before clinical translation.<\/jats:p>","DOI":"10.3390\/genes17040407","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["BRCA1 Promoter CpG Methylation in Breast Cancer: A Pilot Study in African Women"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-7440","authenticated-orcid":false,"given":"Tarryn","family":"Willmer","sequence":"first","affiliation":[{"name":"Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa"},{"name":"Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"},{"name":"Division of Cell Biology, 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\/0000-0002-7156-6699","authenticated-orcid":false,"given":"Mpoi","family":"Makhetha","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Shaik","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa"},{"name":"Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-3396","authenticated-orcid":false,"given":"Lawrence","family":"Mabasa","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa"},{"name":"Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5399-3101","authenticated-orcid":false,"given":"Ines","family":"Buccimazza","sequence":"additional","affiliation":[{"name":"Department of Oncology, Inkosi Albert Luthuli Central Hospital, Durban 4091, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Aldous","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"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. Clin."},{"key":"ref_2","unstructured":"(2025, October 30). World Health OrganizationBreast Cancer [Fact Sheet]. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/breast-cancer."},{"key":"ref_3","unstructured":"Puckett, Y., and Sule, A.A. (2025). Disparity in Early Detection of Breast Cancer. 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