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. 2024 Aug;63(8):e23263.
doi: 10.1002/gcc.23263.

Hereditary Colorectal Cancer and Polyposis Syndromes Caused by Variants in Uncommon Genes

Ahmed Bouras  1   2 , Aurélie Fabre  3 , Hélène Zattara  3 , Sandrine Handallou  4 , Françoise Desseigne  5 , Caroline Kientz  6 , Fabienne Prieur  6 , Magalie Peysselon  7 , Clémentine Legrand  7 , Laura Calavas  8 , Jean-Christophe Saurin  8 , Qing Wang  1   2
Affiliations

Hereditary Colorectal Cancer and Polyposis Syndromes Caused by Variants in Uncommon Genes

Ahmed Bouras et al. Genes Chromosomes Cancer. 2024 Aug.

Abstract

A substantial number of hereditary colorectal cancer (CRC) and colonic polyposis cannot be explained by alteration in confirmed predisposition genes, such as mismatch repair (MMR) genes, APC and MUTYH. Recently, a certain number of potential predisposition genes have been suggested, involving each a small number of cases reported so far. Here, we describe the detection of rare variants in the NTLH1, AXIN2, RNF43, BUB1, and TP53 genes in nine unrelated patients who were suspected for inherited CRC and/or colonic polyposis. Seven of them were classified as pathogenic or likely pathogenic variants (PV/LPV). Clinical manifestations of carriers were largely consistent with reported cases with, nevertheless, distinct characteristics. PV/LPV in these uncommon gene can be responsible for up to 2.7% of inherited CRC or colonic polyposis syndromes. Our findings provide supporting evidence for the role of these genes in cancer predisposition, and contribute to the determination of related cancer spectrum and cancer risk for carriers, allowing for the establishment of appropriate screening strategy and genetic counseling in affected families.

Keywords: cancer predisposition genes; colorectal cancer; polyposis.

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References

    1. L. Valle and K. J. Monahan, “Genetic Predisposition to Gastrointestinal Polyposis: Syndromes, Tumour Features, Genetic Testing, and Clinical Management,” Lancet Gastroenterology & Hepatology 9 (2024): 68–82.
    1. M. Dhooge, S. Baert‐Desurmont, C. Corsini, et al., “National Recommendations of the French Genetics and Cancer Group—Unicancer on the Modalities of Multi‐Genes Panel Analyses in Hereditary Predispositions to Tumors of the Digestive Tract,” European Journal of Medical Genetics 63 (2020): 104080.
    1. R. Mao, P. Krautscheid, R. P. Graham, et al., “Genetic Testing for Inherited Colorectal Cancer and Polyposis, 2021 Revision: A Technical Standard of the American College of Medical Genetics and Genomics (ACMG),” Genetics in Medicine 23 (2021): 1807–1817.
    1. R. M. de Voer, A. Geurts van Kessel, R. D. A. Weren, et al., “Germline Mutations in the Spindle Assembly Checkpoint Genes BUB1 and BUB3 Are Risk Factors for Colorectal Cancer,” Gastroenterology 145 (2013): 544–547.
    1. S. Richards, N. Aziz, S. Bale, et al., “Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology,” Genetics in Medicine 17 (2015): 405–424.

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