尼日利亚乳腺癌患者生殖系BRCA1和BRCA2变异的筛查

IF 2.8 4区 医学 Q3 ONCOLOGY
Technology in Cancer Research & Treatment Pub Date : 2025-01-01 Epub Date: 2025-04-11 DOI:10.1177/15330338251333012
Abimbola F Onyia, Paul Jibrin, Temitope Olatunji-Agunbiade, Ademola Oyekan, AbdulRazzaq Lawal, Adewumi Alabi, Anthonia C Sowunmi, Eben A Aje, Oluwabusayo B Ogunniyi, Ebenezer S Nkom, Opeyemi C De Campos, Oluwakemi A Rotimi, Jelili O Oyelade, Solomon O Rotimi
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引用次数: 0

摘要

背景乳腺癌仍然是尼日利亚妇女死亡的主要原因,其中三阴性乳腺癌(TNBC)尤为普遍。BRCA1和BRCA2基因的变异仍然是这种疾病的关键危险因素。然而,尼日利亚人口中这些变异的频率和频谱存在差距,而且当地缺乏描述这些变异特征的能力。目的本研究旨在鉴定和表征尼日利亚乳腺癌患者和健康年龄匹配对照中BRCA1/2基因的种系变异,以了解该人群乳腺癌的遗传风险概况。方法采用前瞻性病例对照研究,从4家大医院招募乳腺癌患者45例,对照组51例。从血液样本中提取DNA,然后使用Ampliseq BRCA面板和Illumina MiSeq平台对BRCA1/2外显子和内含子区域进行靶向测序。进行变异召唤,在ClinVar和BRCA Exchange数据库中评估临床意义,使用NIH LDlink和Haploview 4.2软件进行单倍型分析。结果6.7%的乳腺癌患者存在致病性BRCA1/2变异,这些患者均为三阴癌且有癌症家族史。检测到两种致病BRCA1变异体:移码缺失BRCA1 c.133_134delAA (p.l ys45fs) (rs397508857)和错读变异体BRCA1 c.5324T > a (p.Met1775Arg) (rs41293463)。BRCA2移码缺失BRCA2 c.8817_8820del (p.l ys2939fs) (rs397508010)也被发现。这些变异在对照组中不存在。单倍型分析显示乳腺癌组存在明显的BRCA1和BRCA2单倍型。结论本研究确定了尼日利亚乳腺癌患者的关键BRCA1/2致病变异和独特的单倍型,强调了人群特异性遗传筛查的必要性。在尼日利亚,将基因检测纳入乳腺癌管理战略可以促进早期发现、个性化治疗计划和遗传咨询。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Screening of Germline BRCA1 and BRCA2 Variants in Nigerian Breast Cancer Patients.

Screening of Germline BRCA1 and BRCA2 Variants in Nigerian Breast Cancer Patients.

Screening of Germline BRCA1 and BRCA2 Variants in Nigerian Breast Cancer Patients.

Screening of Germline BRCA1 and BRCA2 Variants in Nigerian Breast Cancer Patients.

BackgroundBreast cancer remains a leading cause of mortality among Nigerian women, with triple-negative breast cancer (TNBC) being particularly prevalent. Variations in BRCA1 and BRCA2 genes remain key risk factors for this disease. However, there are gaps in the frequency and spectrum of these variants in Nigerian populations, as well as a dearth in the local capacity to characterize these variations.ObjectiveThis study aimed at identifying and characterizing the germline variations in BRCA1/2 in Nigerian breast cancer patients and healthy age-matched controls to understand the genetic risk profile of breast cancer in this population.MethodsA prospective case-control study was conducted involving 45 breast cancer patients and 51 controls recruited from four major hospitals. DNA was extracted from blood samples, followed by targeted sequencing of BRCA1/2 exonic and intronic regions using the Ampliseq BRCA panel and Illumina MiSeq platform. Variant calling was performed, clinical significance was evaluated on ClinVar and BRCA Exchange databases, and haplotype analysis was performed using NIH LDlink and Haploview 4.2 software.ResultsPathogenic BRCA1/2 variants were identified in 6.7% of breast cancer patients, all with TNBC and a family history of cancer. Two pathogenic BRCA1 variants were detected: a frameshift deletion BRCA1 c.133_134delAA (p.Lys45 fs) (rs397508857) and a missense variant BRCA1 c.5324T > A (p.Met1775Arg) (rs41293463). A BRCA2 frameshift deletion BRCA2 c.8817_8820del (p.Lys2939 fs) (rs397508010) was also identified. These variants were absent in controls. Haplotype analysis revealed distinct BRCA1 and BRCA2 haplotypes in the breast cancer group.ConclusionThis study identifies key BRCA1/2 pathogenic variants and unique haplotypes in Nigerian breast cancer patients, highlighting the need for population-specific genetic screening. Integrating genetic testing into breast cancer management strategies could facilitate early detection, personalized treatment planning, and genetic counseling in Nigeria.

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来源期刊
CiteScore
4.40
自引率
0.00%
发文量
202
审稿时长
2 months
期刊介绍: Technology in Cancer Research & Treatment (TCRT) is a JCR-ranked, broad-spectrum, open access, peer-reviewed publication whose aim is to provide researchers and clinicians with a platform to share and discuss developments in the prevention, diagnosis, treatment, and monitoring of cancer.
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