AUTHOR=Gifoni Ana Carolina Leite Vieira Costa , Gifoni Markus Andret Cavalcante , Wotroba Camila Martins , Palmero Edenir Inez , Costa Eduardo Leite Vieira , dos Santos Wellington , Achatz Maria Isabel 

TITLE=Hereditary Breast Cancer in the Brazilian State of Ceará (The CHANCE Cohort): Higher-Than-Expected Prevalence of Recurrent Germline Pathogenic Variants

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.932957

DOI=10.3389/fonc.2022.932957

ISSN=2234-943X

ABSTRACT=<sec><title>Purpose</title><p>There is a significant lack of epidemiological data on hereditary cancer in Northeast Brazil. This is the largest study on the prevalence and mutational spectrum of cancer predisposition genes conducted in this region and the first in the State of Ceará.</p></sec><sec><title>Methods</title><p>Patients ≥18 years of age that were referred to CHANCE (Grupo de Câncer Hereditário do Ceará) from March 2014 to December 2020 with testing criteria for breast cancer susceptibility genes according to NCCN v.1.2021 were eligible to participate. The inclusion of patients was limited to one individual per family and to those born in the State of Ceará. All patients underwent a hereditary cancer panel testing with at least 30 genes.</p></sec><sec><title>Results</title><p>A total of 355 patients were included, and 97 (27.3%) carried a P/LP germline variant in 18 different genes. Among the 97 P/LP carriers, <italic>BRCA1</italic> (31, 31.9%) and <italic>BRCA2</italic> (25, 25.7%) were the most frequently mutated genes, followed by <italic>PALB2</italic> (10, 10.3%), <italic>CHEK2</italic> (7, 7.2%) and <italic>ATM</italic> (4, 4.1%). A small number of recurrent variants (detected in three or more individuals) in <italic>BRCA1</italic>, <italic>BRCA2</italic>, <italic>CHEK2</italic> and <italic>ATM</italic> represented the majority of the P/LP variants described in this cohort.</p></sec><sec><title>Conclusion</title><p>In this cohort, the prevalence of L/PL was high, particularly involving the <italic>BRCA1</italic>, <italic>BRCA2</italic>, <italic>PALB2</italic>, <italic>CHEK2</italic> and <italic>ATM</italic> genes and, to a lesser extent than expected, the <italic>TP53</italic> gene. A high frequency of recurrent variants was also observed, for which further and larger analyses should clarify the presence of any possible founder effect. Characterizing the mutational profile of cancer predisposition genes in diverse populations may contribute to cancer prevention and therapeutic management.</p></sec>