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Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America
npj Breast Cancer ( IF 5.9 ) Pub Date : 2021-08-19 , DOI: 10.1038/s41523-021-00317-6
Josef S Herzog 1 , Yanin Chavarri-Guerra 2 , Danielle Castillo 1 , Julio Abugattas 3 , Cynthia Villarreal-Garza 4, 5 , Sharon Sand 1 , Jessica Clague-Dehart 1, 6 , Rosa M Alvarez-Gómez 5 , Talia Wegman-Ostrosky 5 , Alejandro Mohar 5, 7 , Pamela Mora 3 , Azucena Del Toro-Valero 8 , Adrian Daneri-Navarro 8 , Yenni Rodriguez 9 , Marcia Cruz-Correa 10 , Patricia Ashton-Prolla 11 , Bárbara Alemar 11, 12 , Rosa Mejia 1 , Lenny Gallardo 5 , Robin Shaw 5 , Kai Yang 1 , Aleck Cervantes 1 , Kevin Tsang 1 , Bita Nehoray 1 , Hugo Barrera Saldana 13 , Susan Neuhausen 1 , Jeffrey N Weitzel 14
Affiliation  

The prevalence and contribution of BRCA1/2 (BRCA) pathogenic variants (PVs) to the cancer burden in Latin America are not well understood. This study aims to address this disparity. BRCA analyses were performed on prospectively enrolled Latin American Clinical Cancer Genomics Community Research Network participants via a combination of methods: a Hispanic Mutation Panel (HISPANEL) on MassARRAY; semiconductor sequencing; and copy number variant (CNV) detection. BRCA PV probability was calculated using BRCAPRO. Among 1,627 participants (95.2% with cancer), we detected 236 (14.5%) BRCA PVs; 160 BRCA1 (31% CNVs); 76 BRCA2 PV frequency varied by country: 26% Brazil, 9% Colombia, 13% Peru, and 17% Mexico. Recurrent PVs (seen ≥3 times), some region-specific, represented 42.8% (101/236) of PVs. There was no ClinVar entry for 14% (17/125) of unique PVs, and 57% (111/196) of unique VUS. The area under the ROC curve for BRCAPRO was 0.76. In summary, we implemented a low-cost BRCA testing strategy and documented a significant burden of non-ClinVar reported BRCA PVs among Latin Americans. There are recurrent, population-specific PVs and CNVs, and we note that the BRCAPRO mutation probability model performs adequately. This study helps address the gap in our understanding of BRCA-associated cancer in Latin America.



中文翻译:

拉丁美洲 BRCA1 和 BRCA2 相关癌症的遗传流行病学

BRCA1 / 2 ( BRCA ) 致病性变异 (PV) 对拉丁美洲癌症负担的患病率和贡献尚不清楚。本研究旨在解决这种差异。通过多种方法对前瞻性登记的拉丁美洲临床癌症基因组学社区研究网络参与者进行BRCA分析:MassARRAY 上的西班牙裔突变小组 ( HISPANEL );半导体测序;和拷贝数变异(CNV)检测。使用 BRCAPRO 计算BRCA PV 概率。在 1,627 名参与者(95.2% 患有癌症)中,我们检测到 236(14.5%)个 BRCA PV;160 BRCA1(31% CNV);76 BRCA2PV 频率因国家/地区而异:巴西 26%、哥伦比亚 9%、秘鲁 13% 和墨西哥 17%。复发性 PV(见 ≥3 次),某些区域特定,占 PV 的 42.8% (101/236)。14% (17/125) 的独特 PV 和 57% (111/196) 的独特 VUS 没有 ClinVar 条目。BRCAPRO 的 ROC 曲线下面积为 0.76。总之,我们实施了低成本BRCA测试策略,并记录了拉丁美洲非 ClinVar 报告的BRCA PV的重大负担。有反复出现的、特定于人群的 PV 和 CNV,我们注意到 BRCAPRO 突变概率模型表现良好。这项研究有助于解决我们对拉丁美洲BRCA相关癌症的理解差距。

更新日期:2021-08-19
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