Department of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.
Medical Genetics Laboratory, Tor Vergata Hospital, Rome, Italy.
Hum Genomics. 2021 Oct 30;15(1):65. doi: 10.1186/s40246-021-00365-w.
Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among women in Africa after cervical cancer. Even if the epidemiological data are now aligned with those relating to industrialized countries, the knowledge concerning breast cancer in Africa, particularly in Western Africa, still lack clinical data, medical treatments, and the evaluation of genetic and non-genetic factors implicated in the etiology of the disease. The early onset and the aggressiveness of diagnosed breast cancers in patients of African ancestry strongly suggest that the genetic risk factor may be a key component, but so far, very few studies on the impact of germ line mutations in breast cancer in Africa have been conducted, with negative consequences on prevention, awareness and patient management. Through Next Generation sequencing (NGS), we analyzed all of the coding regions and the exon-intron junctions of BRCA1 and BRCA2 genes-the two most important genes in hereditary breast cancer-in fifty-one women from Burkina Faso with early onset of breast cancer with or without a family history.
We identified six different pathogenic mutations (three in BRCA1, three in BRCA2), two of which were recurrent in eight unrelated women. Furthermore, we identified, in four other patients, two variants of uncertain clinical significance (VUS) and two variants never previously described in literature, although one of them is present in the dbSNP database.
This is the first study in which the entire coding sequence of BRCA genes has been analyzed through Next Generation Sequencing in Burkinabe young women with breast cancer. Our data support the importance of genetic risk factors in the etiology of breast cancer in this population and suggest the necessity to improve the genetic cancer risk assessment. Furthermore, the identification of the most frequent mutations of BRCA1 and BRCA2 in the population of Burkina Faso will allow the development of an inexpensive genetic test for the identification of subjects at high genetic cancer risk, which could be used to design personalized therapeutic protocols.
乳腺癌（BC）是非洲女性中最常见的癌症，也是仅次于宫颈癌的第二大癌症相关死亡原因。即使现在的流行病学数据与工业化国家的数据相符，但非洲，特别是西非，关于乳腺癌的知识仍然缺乏临床数据、医疗方法，以及对疾病病因学中涉及的遗传和非遗传因素的评估。非洲裔患者乳腺癌的早期发病和侵袭性强烈表明遗传风险因素可能是一个关键组成部分，但到目前为止，针对非洲乳腺癌中种系突变影响的研究非常少，这对预防、意识和患者管理都产生了负面影响。通过下一代测序（NGS），我们分析了来自布基纳法索的 51 名具有早发性乳腺癌的女性（有或无家族史）的 BRCA1 和 BRCA2 基因的所有编码区域和外显子-内含子接头，这两个基因是遗传性乳腺癌中最重要的两个基因。
我们发现了六个不同的致病性突变（BRCA1 中有三个，BRCA2 中有三个），其中两个在八个无亲缘关系的女性中反复出现。此外，我们在另外四名患者中发现了两个意义未明的变异体（VUS）和两个以前从未在文献中描述过的变体，尽管其中一个变体存在于 dbSNP 数据库中。
这是第一项通过下一代测序分析布基纳法索年轻乳腺癌女性 BRCA 基因全部编码序列的研究。我们的数据支持遗传风险因素在该人群乳腺癌发病机制中的重要性，并表明有必要改进遗传癌症风险评估。此外，确定 BRCA1 和 BRCA2 在布基纳法索人群中的最常见突变将有助于开发一种廉价的遗传测试，以识别具有高遗传癌症风险的个体，从而可以设计个性化的治疗方案。
