Latin American Study of Hereditary Breast and Ovarian Cancer LACAM : A Genomic Epidemiology Approach

• Published in: Frontiers in oncology Vol. 9; p. 1429
• Main Authors: 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, Nuñez Castillo, Johanna, Frecha, Cecilia, Riggi, Cecilia, Jauk, Federico, Gómez García, Eva María, Carranza, Claudia Lorena, Zamora, Vanessa, Torres Mejía, Gabriela, Romieu, Isabelle, Castañeda, Carlos Arturo, Castillo, Miluska, Gitler, Rina, Antoniano, Adriana, Rojas Jiménez, Ernesto, Romero Cruz, Luis Enrique, Vallejo Lecuona, Fernando, Delgado Enciso, Iván, Martínez Rizo, Abril Bernardette, Flores Carranza, Alejandro, Benites Godinez, Verónica, Méndez Catalá, Claudia Fabiola, Herrera, Luis Alonso, Chirino, Yolanda Irasema, Terrazas, Luis Ignacio, Perdomo, Sandra, Vaca Paniagua, Felipe
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.12.2019
• Subjects: breast cancer susceptibility; germline pathogenic variants; HBOC; Latin America; massively parallel sequencing; Oncology; germline pathogenic variants; breast cancer susceptibility; massively parallel sequencing; HBOC; Latin America
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2019.01429

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. 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. 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 (20%) and (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as , and . Additional pathogenic variants were found in HBOC unrelated genes such as , and . 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.