Genotype–Phenotype Correlations in Autosomal Dominant and Recessive APC Mutation-Negative Colorectal Adenomatous Polyposis

Abstract

The most prevalent type of intestinal polyposis, colorectal adenomatous polyposis (CAP), is regarded as a precancerous lesion of colorectal cancer with obvious genetic characteristics. Early screening and intervention can significantly improve patients’ survival and prognosis. The adenomatous polyposis coli ( APC ) mutation is believed to be the primary cause of CAP. There is, however, a subset of CAP with undetectable pathogenic mutations in APC , known as APC (-)/CAP. The genetic predisposition to APC (-)/CAP has largely been associated with germline mutations in some susceptible genes, including the human mutY homologue (MUTYH) gene and the Nth-like DNA glycosylase 1 (NTHL1) gene, and DNA mismatch repair (MMR) can cause autosomal recessive APC (-)/CAP. Furthermore, autosomal dominant APC (-)/CAP could occur as a result of DNA polymerase epsilon ( POLE )/DNA polymerase delta 1 ( POLD1 ), axis inhibition protein 2 ( AXIN2 ), and dual oxidase 2 ( DUOX2 ) mutations. The clinical phenotypes of these pathogenic mutations vary greatly depending on their genetic characteristics. Therefore, in this study, we present a comprehensive review of the association between autosomal recessive and dominant APC (-)/CAP genotypes and clinical phenotypes and conclude that APC (-)/CAP is a disease caused by multiple genes with different phenotypes and interaction exists in the pathogenic genes.

Cancer Predisposition Syndromes and Thyroid Cancer: Keys for a Short Two-Way Street

“…Other manifestations include sebaceous adenomas, thyroid nodules, CHRPE, adrenal lesions, and mandibular cysts [ 22 ]. The risk of thyroid malignancy in FAP2 is still unclear, although a few cases of papillary thyroid cancer have been reported [ 23 ].…”