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

<b>Purpose:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 <i>BRCA1</i> (20%) and <i>BRCA2</i> (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as <i>MSH2, MSH6, MUTYH</i>, and <i>PALB2</i>. Additional pathogenic variants were found in HBOC unrelated genes such as <i>DCLRE1C, WRN, PDE11A</i>, and <i>PDGFB</i>. <b>Conclusion:</b> 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.