Prevalence of pathogenic germline variants in hereditary breast/ovarian cancer patients at the National Cancer Genetic Counseling Center in Costa Rica.

Abstract

e17567 Background: There is limited information on pathogenic germline variants prevalence in Hereditary Breast/Ovarian Cancer (HBOC) across the Central America region. This study assessed the pathogenic variants prevalence among patients with HBOC, who were referred according to the pre-established referral criteria at the National Cancer Genetic Counseling Center of the Social Security of Costa Rica (Caja Costarricense de Seguro Social, CCSS). Methods: A descriptive, observational, cross-sectional study in a group of 792 unrelated HBOC patients who were tested 58-gene next-generation sequencing (NGS) panel testing, between August 2019 and December 2023 was performed. Sociodemographic and clinical characteristics were summarized using descriptive statistics. The association of each criterion and the tumor immunophenotype with the presence of Pathogenic/likely pathogenic germline variants (PGVs) in clinically actionable cancer genes was assessed by computing odds ratios (OR) and 95% confidence intervals (CI). The overall capacity to predict the presence of PGVs in those genes by combining all predefined criteria was explored with a multivariate logistic regression model, computing the area under the curve (AUC) in the test set (20% of the data). All calculations, table generation, and graphics were conducted using Python version 3.8.10. Results: Among the whole group, the mean age at testing was 47.3. PGVs were identified in 212 (26.8%) of probands. The highest frequency of PGVs was in genes BRCA2 (56.1%), ATM (13.7%) and BRCA1 (8.5%). The most common pathogenic variant in the BRCA2 gen (c.9235deIG), found in 52.4% of probands with BRCA2 PGVs, highlighting ethnic differences in Costa Rican patients and suggesting a founder pathogenic variant. Also, two novel pathogenic variants were detected in BRCA2 gen. BRCA2 variants were not associated with any specific immunophenotype (OR:0.82, 95% CI 0.51-1.32). The pre-established criteria where adequate to predict the presence of a PGV (AUC 0.74), individually exhibited limited association. Conclusions: This study reported a relatively high prevalence of PGVs in BRCA2 and ATM genes among HBOC patients in Costa Rica, emphasizing the genetic heterogeneity within the Costa Rican population and recognizing the crucial role of genetic counseling and testing.