Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis

Abstract

Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-β, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation.

Screening for Mutations in Hereditary Cancer Susceptibility Genes in a Region with High Endogamy in Brazil

“…However, in addition to these, other extraintestinal manifestations can occur in patients with MAP, including skin findings (benign and malignant). 19 20 In a cohort of patients with MAP followed up, the occurrence of extraintestinal tumors and skin cancer was the second most common cancer reported, with a significant incidence (standardized incidence ratio: 2.8; 95% confidence interval: 1.5–4.8). In that study, of the 13 patients with skin cancer, 5 had the p.Gly396Asp mutation and of these, 2 were diagnosed with melanoma.…”

A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population

“…In addition, 13 variants, mostly pathogenic, were found in the APC gene. Familial adenomatous polyposis (FAP), characterized by the presence of dozens to hundreds of colorectal adenomas, is a hereditary disease caused by germline variants in APC , a key tumor suppressor gene in the regulation of the WNT signaling pathway [ 35 , 39 ]. FAP patients have a high risk of developing colorectal cancer, and an increased risk of gastric, small bowel, pancreatic, and thyroid carcinoma, in addition to bone and ophthalmological alterations [ 39 ].…”

“…Familial adenomatous polyposis (FAP), characterized by the presence of dozens to hundreds of colorectal adenomas, is a hereditary disease caused by germline variants in APC , a key tumor suppressor gene in the regulation of the WNT signaling pathway [ 35 , 39 ]. FAP patients have a high risk of developing colorectal cancer, and an increased risk of gastric, small bowel, pancreatic, and thyroid carcinoma, in addition to bone and ophthalmological alterations [ 39 ]. In this cohort, 11 of the variants were identified in patients diagnosed with colorectal cancer, but without polyps or other clinical manifestation of FAP.…”