Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America
Por:
Herzog J.S., Chavarri-Guerra Y., Castillo D., Abugattas J., Villarreal-Garza C., Sand S., Clague-Dehart J., Alvarez-Gómez R.M., Wegman-Ostrosky T., Mohar A., Mora P., 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.
Publicada:
1 ene 2021
Resumen:
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. © 2021, The Author(s).
Filiaciones:
Herzog J.S.:
City of Hope, Duarte, CA, United States
Chavarri-Guerra Y.:
Instituto Nacional de Ciencias Médicas Y Nutrición, Salvador Zubirán, México City, Mexico
Castillo D.:
City of Hope, Duarte, CA, United States
Abugattas J.:
Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru
Villarreal-Garza C.:
Hospital Zambrano Hellion TecSalud, Tecnologico de Monterrey, Monterrey, Mexico
Instituto Nacional de Cancerología, Mexico City, Mexico
Sand S.:
City of Hope, Duarte, CA, United States
Clague-Dehart J.:
City of Hope, Duarte, CA, United States
School of Community & Global Health, Claremont Graduate University, Claremont, CA, United States
Alvarez-Gómez R.M.:
Instituto Nacional de Cancerología, Mexico City, Mexico
Wegman-Ostrosky T.:
Instituto Nacional de Cancerología, Mexico City, Mexico
Mohar A.:
Instituto de Investigaciones Biomédicas, Mexico City, Mexico
Instituto Nacional de Cancerología, Mexico City, Mexico
Mora P.:
Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru
Del Toro-Valero A.:
Instituto Jalisciense de Cancerología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, México City, Mexico
Daneri-Navarro A.:
Instituto Jalisciense de Cancerología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, México City, Mexico
Rodriguez Y.:
Centro de Oncologia, Clínica del Country, Bogotá, Colombia
Cruz-Correa M.:
University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
Ashton-Prolla P.:
Hospital de Clínicas de Porto Alegre and Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Alemar B.:
Hospital de Clínicas de Porto Alegre and Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Roche Pharmaceutical, Basel, Switzerland
Mejia R.:
City of Hope, Duarte, CA, United States
Gallardo L.:
Instituto Nacional de Cancerología, Mexico City, Mexico
Shaw R.:
Instituto Nacional de Cancerología, Mexico City, Mexico
Yang K.:
City of Hope, Duarte, CA, United States
Cervantes A.:
City of Hope, Duarte, CA, United States
Tsang K.:
City of Hope, Duarte, CA, United States
Nehoray B.:
City of Hope, Duarte, CA, United States
Barrera Saldana H.:
Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico
Neuhausen S.:
City of Hope, Duarte, CA, United States
Weitzel J.N.:
Latin American School of Oncology (Escuela Latinoamericana de Oncología), Tuxla Gutiérrez, Chiapas, Mexico
All Open Access; Gold
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