Ann Coloproctol.
2021 Dec;37(6):368-381. 10.3393/ac.2021.00878.0125.
Genotypic and Phenotypic Characteristics of Hereditary Colorectal Cancer
- Affiliations
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- 1Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
- 2Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
- 3Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
- KMID: 2523365
- DOI: http://doi.org/10.3393/ac.2021.00878.0125
Abstract
- The genomic causes and clinical manifestations of hereditary colorectal cancer (HCRC) might be stratified into 2 groups, namely, familial (FCRC) and a limited sense of HCRC, respectively. Otherwise, FCRC is canonically classified into 2 major categories; Lynch syndrome (LS) or associated spectra and inherited polyposis syndrome. By contrast, despite an increasing body of genotypic and phenotypic traits, some FCRC cannot be clearly differentiated as definitively single type, and the situation has become more complex as additional causative genes have been discovered. This review provides an overview of HCRC, including 6 LS or associated spectra and 8 inherited polyposis syndromes, according to molecular pathogenesis. Variants and newly-identified FCRC are particularly emphasized, including MUTYH (or MYH)-associated polyposis, Muir-Torre syndrome, constitutional mismatch repair deficiency, EPCAM-associated LS, polymerase proofreading-associated polyposis, RNF43- or NTHL1-associated serrated polyposis syndrome, PTEN hamartoma tumor syndrome, and hereditary mixed polyposis syndrome. We also comment on the clinical utility of multigene panel tests, focusing on comprehensive cancer panels that include HCRC. Finally, HCRC surveillance strategies are recommended, based on revised or notable concepts underpinned by competent validation and clinical implications, and favoring major guidelines. As hereditary syndromes are mainly attributable to genomic constitutions of distinctive ancestral groups, an integrative national HCRC registry and guideline is an urgent priority.
