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Analysis of germline genetic variants that cause hereditary coloretal cancer in Bahia

Miguel, D. S. C. G.; Costa, L. C.; Alves, M. E. A. V.; Cerqueira, P. M.; de Carvalho, R. N.; Sampaio, R. A.; Carvalho, D. B. O. D.; Carvalho, R. h.; de Castro, I. C. S.

2024-12-08 genetic and genomic medicine
10.1101/2024.12.06.24318416 medRxiv
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BackgroundColorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Approximately 10% of CRC cases are linked to hereditary germline variants. Understanding regional genetic predispositions is crucial for developing personalized medicine strategies. ObjectiveThis study aims to analyze pathogenic germline variants associated with polyposis and non-polyposis syndromes in individuals from Bahia, Brazil. MethodsA cross-sectional, observational study was conducted on 3,100 probands from a private laboratory in Salvador, Bahia, between August 2017 and February 2023. Probands underwent Next Generation Sequencing (NGS) targeting 37 genes. Variants classified as pathogenic (P) or probably pathogenic (PP) in 11 high/moderate penetrance genes were analyzed. ResultsAmong the 3,100 probands, 97 (3.12%) had P/PP variants. Polyposis syndromes accounted for 47 cases (1.51%), with prevalent variants in MUTYH, APC, and PTEN genes. Non-polyposis (Lynch) syndrome was observed in 50 cases (1.61%), predominantly involving MSH2 and MLH1 genes. Notably, a novel variant, MLH1 c.1127_1130dup, was identified. ConclusionThis study highlights the genetic diversity in CRC predisposition in Bahia, emphasizing the need for targeted regional genetic screening and personalized healthcare strategies. Identifying recurrent pathogenic variants suggests possible shared ancestry among individuals, offering insights for future genetic counseling and public health policies.

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