BRIEF RESEARCH REPORT article
Front. Cancer Control Soc.
Sec. Social Determinants in Cancer
Volume 3 - 2025 | doi: 10.3389/fcacs.2025.1549584
This article is part of the Research TopicCancer Epidemiology and Etiology Evaluation in Latin American PopulationView all 6 articles
Impact of Germline Panel Size on Hereditary Cancer: Findings of Variants of Uncertain Significance (VUS) in the Brazilian Public Health Population Selected for High Hereditary Cancer Risk
Provisionally accepted
Christine Alem*
Barbara Narciso Duarte
Cabello A.E.R.S.Sandra Regina Campos TeixeiraThiago GasparMarcio Lopes de SouzaCesar Cabello- State University of Campinas, Campinas, Brazil
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Breast cancer remains the most prevalent malignant neoplasm among Brazilian women, excluding non-melanoma skin cancers, with a notable proportion of hereditary cases linked to pathogenic or likely pathogenic germline variants (PV/LPV). This cross-sectional study aimed to evaluate epidemiological and reproductive factors, as well as the impact of multigene panel size on the detection of variants of uncertain significance (VUS), which pose challenges for genetic counseling and clinical decision-making. Between November 2021 and October 2022, 364 women meeting NCCN 2022 criteria were recruited from the High-Risk Outpatient Clinic at the Women's Hospital Prof. José Aristodemo Pinotti – CAISM, UNICAMP. Germline DNA was analyzed via next-generation sequencing (NGS) across 144 genes associated with hereditary cancer syndromes. Statistical analyses included Chi-Square, Fisher’s Exact, Kruskal-Wallis, Bowker, McNemar, and stepwise logistic regression (significance: p<0.05). Of the patients, 86% exhibited genetic alterations, with a high prevalence of VUS, particularly in the ATM gene. No significant associations were found between VUS presence and reproductive or epidemiological variables. Notably, the 144-gene panel yielded a significantly higher VUS detection rate (56.3%) compared to smaller panels of 20 (23.9%) and 23 genes (31%) (p<0.001), without a proportional increase in PV/LPV identification. These findings emphasize the need for optimized panel design tailored to genetically diverse populations, such as Brazil’s, to balance comprehensive variant detection with clinical utility. The study reinforces the complexity of interpreting VUS and the importance of refining genetic testing strategies in hereditary breast cancer care.
Keywords: high risk, germline mutations, Genetic Testing, Breast câncer, Variants of uncertain significance (VUS)
Received: 16 Jan 2025; Accepted: 25 Aug 2025.
Copyright: © 2025 Alem, Duarte, A.E.R.S., Teixeira, Gaspar, de Souza and Cabello. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Christine Alem, State University of Campinas, Campinas, Brazil
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