Department of Clinical Medicine, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Department of Genetics, Inkosi Albert Luthuli Central Hospital, Durban, South Africa.
S Afr Med J. 2024 May 31;114(6):e1094. doi: 10.7196/SAMJ.2024.v114i6.1094.
Hereditary breast cancer is characterised by the presence of a pathogenic sequence variant passed from one generation to the next. These cancers are aggressive, develop early, and account for 5 - 10% of all breast cancer cases. In South Africa (SA), the common variants that predispose to hereditary breast cancer have been well documented among white patients and form part of screening panels during targeted testing. For non-white patients, common variants are not well understood, and as such, all populations are offered the same test optimised for white patients. This carries a risk of misdiagnosis, the consequences of which include recurrence and increased mortality.
To retrospectively describe genetic trends in the black African and Indian breast cancer patients from KwaZulu-Natal Province, SA.
We reviewed clinical and genetic data of breast cancer and high-risk patients who consulted at Inkosi Albert Luthuli Central Hospital between 2011 and 2021. Inclusion criteria were based on clinical and demographic characteristics as defined by SA clinical guidelines.
Black African patients were young (mean 37.6 years, standard deviation 11.16) and had the majority of triple-negative tumours (37.5%). Indians represented 50% of bilateral breast cancers and of high-risk individuals. We identified 30 pathogenic BRCA1/2 sequence variants, four large genomic rearrangements and 13 variants of unknown significance. Twenty black patients carried 12, 13 white patients carried 4, 25 Indian patients carried 16, and 3 coloured patients carried 3 pathogenic sequence variants. The most frequent variants were BRCA2 c.5771_5774del, p.Ile1924fs among black patients, BRCA2 c.7934del, p.Arg2645fs among white patients, and BRCA2 c.8754+1G>A among Indian patients. None of the founder mutations common in white patients was reported in either black, Indian or coloured patients, which explains why black, Coloured and Indian SA patients consistently test negative during targeted screening.
This study highlights unique genetic trends for SA populations and the need for more inclusive targeted tests that are optimal for these populations.
遗传性乳腺癌的特征是存在从一代传递到下一代的致病性序列变异。这些癌症具有侵袭性，早期发展，并占所有乳腺癌病例的 5-10%。在南非（SA），已对白种患者中易患遗传性乳腺癌的常见变异进行了很好的记录，并构成了靶向测试中筛查小组的一部分。对于非白种患者，常见变异尚不清楚，因此，所有人群都接受了针对白种患者优化的相同测试。这存在误诊的风险，其后果包括复发和死亡率增加。
回顾性描述南非夸祖鲁-纳塔尔省黑人和印度裔乳腺癌患者的遗传趋势。
我们回顾了 2011 年至 2021 年间在因科西·阿尔伯特·卢图利中央医院就诊的乳腺癌和高风险患者的临床和遗传数据。纳入标准基于南非临床指南定义的临床和人口统计学特征。
黑种人患者年轻（平均 37.6 岁，标准差 11.16），大多数为三阴性肿瘤（37.5%）。印度人占双侧乳腺癌和高风险人群的 50%。我们发现了 30 个致病性 BRCA1/2 序列变异、4 个大片段基因组重排和 13 个意义不明的变异。20 名黑人患者携带 12 个、13 名白人患者携带 4 个、25 名印度患者携带 16 个和 3 名有色人种患者携带 3 个致病性序列变异。最常见的变异是黑人患者中的 BRCA2 c.5771_5774del，p.Ile1924fs，白人患者中的 BRCA2 c.7934del，p.Arg2645fs，印度患者中的 BRCA2 c.8754+1G>A。在黑人、印度或有色人种患者中均未报告白人患者中常见的任何启动子突变，这解释了为什么南非的黑人、有色人种和印度人在靶向筛查中始终呈阴性。
本研究强调了南非人群独特的遗传趋势，以及需要针对这些人群进行更具包容性的靶向测试。
