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.
Highlights
Breast and ovarian cancers have been recognized as heterogeneous diseases comprising several molecular subtypes, each one with an associated risk profile and specific treatment recommendations [1,2,3]
Uruguay (20.5), Argentina (19.4), and Cuba (14.9) show the higher rates whereas Guatemala (3.9) and El Salvador (4.1) show the lowest [9]. Both incidence and mortality proportions for Latin American women aged under 44 years have been shown to be higher when compared with those found in high income countries (20 vs. 12% and 14 vs. 7%, respectively), suggesting an important contribution in LA of prevalent risk factors and genetic background [11]
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)
Summary
Breast and ovarian cancers have been recognized as heterogeneous diseases comprising several molecular subtypes, each one with an associated risk profile and specific treatment recommendations [1,2,3]. Latin America (LA) is a region encompassing 33 countries, with diverse culture, geography, and ethnicity. The highest standardized incidence rates of breast cancer by age are present in Argentina, Brazil and Uruguay (between 67.7 and 71.9) and the lowest in Bolivia (12.7) and El Salvador (7.9). Uruguay (20.5), Argentina (19.4), and Cuba (14.9) show the higher rates whereas Guatemala (3.9) and El Salvador (4.1) show the lowest [9] Both incidence and mortality proportions for Latin American women aged under 44 years have been shown to be higher when compared with those found in high income countries (20 vs 12% and 14 vs 7%, respectively), suggesting an important contribution in LA of prevalent risk factors and genetic background [11]
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