Title
Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America
Date Issued
01 December 2021
Access level
open access
Resource Type
journal article
Author(s)
Herzog J.S.
Chavarri-Guerra Y.
Castillo D.
Villarreal-Garza C.
Sand S.
Clague-Dehart J.
Alvarez-Gómez R.M.
Wegman-Ostrosky T.
Mohar A.
Del Toro-Valero A.
Daneri-Navarro A.
Rodriguez Y.
Cruz-Correa M.
Ashton-Prolla P.
Alemar B.
Mejia R.
Gallardo L.
Shaw R.
Yang K.
Cervantes A.
Tsang K.
Nehoray B.
Barrera Saldana H.
Neuhausen S.
Weitzel J.N.
Publisher(s)
Springer Nature Limited
Nature Research
Abstract
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.
Volume
7
Issue
1
Language
English
OCDE Knowledge area
Oncología
Scopus EID
2-s2.0-85113223709
Source
npj Breast Cancer
ISSN of the container
23744677
Sponsor(s)
Funding for this work was kindly provided by the Breast Cancer Research Foundation BCRF (BCRF-19–172; 20-172); AVON Foundation for Women (Grant No. 02–2013–044); the American Cancer Society (ACS) (ID No. RSGT-10–203–01-CPPB); Conquer Cancer Research Professorship in Breast Cancer Disparities (JNW), R25CA171998 (co-PIs: K. Blazer and J. Weitzel), R25CA085771 (support for J. Clague). City of Hope Clinical Cancer Genomics Community Research Network was also supported in part by Award Number RC4CA153828 (PI: JNW) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The research reported in this publication included work performed in the Integrated Genomics Core at City of Hope supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572, as well as a supplement award titled: Strengthening capacity to promote genomic cancer risk assessment dissemination and implementation research and translation among underserved populations in the Americas. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CNPq Brazil Grant No. 408313/2016–1 (Patricia Ashton-Prolla) and CNPq Brazil doctoral fellowship granted to Barbara Alemar. We acknowledge all of our CCGCRN collaborators from Latin America, especially Luis Herrera, Jazmin Arteaga, Dione Aguilar, and Sandra Franco. We thank Thomas Slavin for his collaboration on variant curation.
Sources of information:
Directorio de Producción Científica
Scopus