Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis
by
, , and
Diana Haimov
1, 
Sari Lieberman
2,
Sergi Castellvi-Bel
3
,
Maartje Nielsen
4 and
Yael Goldberg
1,5,*
1
Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petach-Tikva 4941492, Israel
2
Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
3
Department of Gastroenterology, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Clínic, 08035 Barcelona, Spain
4
Department of Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
5
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
*
Author to whom correspondence should be addressed.
Cancers 2022, 14(3), 628; https://doi.org/10.3390/cancers14030628
Submission received: 29 December 2021
/
Revised: 22 January 2022
/
Accepted: 23 January 2022
/
Published: 26 January 2022
(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)
Simple Summary
Familiarity with nonmalignant features and comorbidities of cancer predisposition syndromes may raise awareness and assist clinicians in the diagnosis and interpretation of molecular test results. Genetic predisposition to colorectal cancer (CRC) should be suspected mainly in young patients, in patients with significant family histories, multiple polyps, mismatch repair-deficient tumors, and in association with malignant or nonmalignant comorbidities. The aim of this review is to describe the main nonmalignant comorbidities associated with selected CRC predisposition syndromes that may serve as valuable diagnostic clues for clinicians and genetic professionals.
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.
Keywords:
colorectal cancer; genetic predisposition; diagnosis; extracolonic; germline; mosaicism; mTOR polyposis; TGF-β; WNT
