Frequency and spectrum of BRCA pathogenic/likely pathogenic variants in the Hispanic population of south Florida: A retrospective analysis.

Abstract

10579 Background: The genetic landscape of hereditary breast and ovarian cancer in diverse populations remains underexplored, particularly within Hispanic/Latino communities. While BRCA1 and BRCA2 pathogenic and likely pathogenic (P/LP) variants are well-studied in some ethnic groups, data on Hispanic populations with varied ancestries is limited. South Florida’s unique demographic, characterized by a large Hispanic population with ancestries from the Caribbean, Central, and South America, provides an opportunity to examine the prevalence and spectrum of BRCA1 and BRCA2 variants in this group. Methods: Data was extracted from Progeny and Cerner PowerChart and de-identified in MS Excel. The cohort consists of individuals who underwent germline genetic testing (ranging from single site to multigene panels) at Miami Cancer Institute's Clinical Genetics clinic from 01/01/2017 to 07/08/2022 with a personal/family history of breast and/or ovarian cancer. The sample was categorized by self-reported race, ethnicity, and ancestry, with a focus on White, Black, and Hispanic/Latino categories. We compared BRCA1 and BRCA2 P/LP variants across race/ethnicity. Results: A total of 3,784 cases were reviewed, predominantly female (97.6%), with 73.6% (n = 2786) affected by breast cancer. The median age was 54 years (range: 20-92). Most of the population identified as Hispanic/Latino (65%, n = 2,460), with Cuban ancestry reported most frequently on both maternal (38.4%) and paternal (37.3%) sides. The prevalence of BRCA1 and BRCA2 P/LP variants in Hispanic/Latino individuals was 5.1% (126 of 2460), with the majority having a BRCA2 variant (n = 86; 68.2%). Variants of uncertain significance were observed in 3.4% of the Hispanic population. The most frequent P/LP variants in BRCA1 included c.211A > G (n = 5, 12.5%) and c.3331_3334delCAAG (n = 3, 7.5%). In BRCA2 , common P/LP variants were c.771_775del (n = 8, 9.3%), c.2808_2811del (n = 6, 7%), c.5799_5802del and c.9235delG (each n = 5, 5.8%), and c.5073dupA (n = 4; 4.6%). Conclusions: This cohort revealed a variety of unique P/LP variants in BRCA1 (n = 31) and BRCA2 (n = 56), reflecting the genetic diversity in this population. Other cancer susceptibility gene P/LP variants were noted but were not the focus of the study. Notably, BRCA2 c.771_775del (n = 8), an established Icelandic founder variant not reported to be recurrent in Hispanics, was only observed in those of Cuban/Spaniard ancestry in this cohort. Other variants, such as c.9235delG and c.5073dupA in BRCA2 , were identified in Nicaraguan and Cuban populations for the first time. The study also highlighted common founder and recurrent variants in European, Caribbean, Central, and South American populations. South Florida’s Hispanic population, including individuals from underrepresented regions, offers a rich and unique dataset of BRCA1 and BRCA2 P/LP variants.