1. Latin American Study of Hereditary Breast and Ovarian Cancer LACAM : A Genomic Epidemiology Approach.
- Author
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Oliver, Javier, Quezada Urban, Rosalía, Franco Cortés, Claudia Alejandra, Díaz Velásquez, Clara Estela, Montealegre Paez, Ana Lorena, Pacheco-Orozco, Rafael Adrián, Castro Rojas, Carlos, García-Robles, Reggie, López Rivera, Juan Javier, Gaitán Chaparro, Sandra, Gómez, Ana Milena, Suarez Obando, Fernando, Giraldo, Gustavo, Maya, Maria Isabel, Hurtado-Villa, Paula, Sanchez, Ana Isabel, Serrano, Norma, Orduz Galvis, Ana Isabel, Aruachan, Sandra, and Nuñez Castillo, Johanna
- Subjects
HEREDITARY cancer syndromes ,BREAST cancer ,OVARIAN cancer ,LATIN American studies ,HEALTH facilities ,EPIDEMIOLOGY - Abstract
Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5–10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH , and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A , and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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