Hereditary Colorectal Polyposis and Cancer Syndromes: A Primer on Diagnosis and Management

Abstract

Colorectal cancer (CRC) is the fourth most common cancer amongst men and women. Between 3 and 6% of all CRCs are attributed to well-defined inherited syndromes, including Lynch syndrome, familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and several hamartomatous polyposis conditions. Identification of these patients through family history and appropriate genetic testing can provide estimates of cancer risk that inform appropriate cancer screening, surveillance and/or preventative interventions. This narrative review examines the hereditary colorectal cancer and polyposis syndromes, their genetic basis, clinical management, and evidence supporting cancer screening.

Hereditary Cancer Syndromes—A Primer on Diagnosis and Management

“…It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Learning Objectives: On completion of this article, you should be able to (1) differentiate between the most common clinically encountered hereditary colorectal cancer and polyposis syndromes, (2) recognize the genetic cause and associated cancer risk with these syndromes, and (3) apply cancer screening/surveillance recommendations in this high-risk population. Disclosures: As a provider accredited by ACCME, Mayo Clinic College of Medicine and Science (Mayo School of Continuous Professional Development) must ensure balance, independence, objectivity, and scientific rigor in its educational activities.…”

“…High-risk hereditary predisposition syndromes have been associated with a 60% to 100% lifetime risk of development of colorectal cancers and breast-ovarian cancers. 1 Many people also carry an increased risk of several other cancers. Given the markedly increased risk of cancer, patients with a genetic predisposition are advised to follow a rigorous surveillance protocol managed by genetic counselors.…”

Molecular Diagnostics in Clinical Oncology

“…For example, the analysis of mutations related to breast cancer risk would include BRCA1, BRCA2, PALB2, TP53, CHEK2, ATM, NBS/NBN, BLM, PTEN, MRE11, BRIP1, BARD1, RAD50, RAD51C, RAD51D, RECQL, FANCC, FANCM and perhaps some other genes (Sokolenko et al, 2012; Thompson et al, 2012; Kiiski et al, 2014; Kurian et al, 2014; Cybulski et al, 2015; Easton et al, 2015). Similarly, genetic testing for HNPCC requires the analysis of MLH1, MSH2, MSH6, PMS2 , and EPCAM coding sequences, while the panel for diagnosis of colon polyposis would involve APC, MUTYH, NTHL1, POLE, POLD1, SMAD4, BMPR1A, STK11 , and MSH3 (Weren et al, 2015; Adam et al, 2016; Bellido et al, 2016; Kanth et al, 2017). Valid conclusions on the lack of causative mutation cannot be made solely on the basis of Sanger sequencing; it is often somehow overlooked, that many germ-line mutations are represented by large gene rearrangements (LGRs), which require distinct diagnostic platforms, e.g., multiplex ligation-dependent probe amplification (MLPA) or droplet digital PCR (ddPCR) (Ewald et al, 2009; Sluiter and van Rensburg, 2011; Preobrazhenskaya et al, 2017).…”

Telephone versus in‐person colorectal cancer risk and screening intervention for first‐degree relatives: A randomized controlled trial

“…A family history of CRC is a critical risk factor for developing the disease. Approximately 5% to 10% of CRC cases are due to inherited syndromes, and 25% of CRC cases occur in individuals with at least 1 first‐degree relative (FDR) with CRC . However, CRC screening rates rarely exceed 50% among FDRs of patients with CRC …”

“…Approximately 5% to 10% of CRC cases are due to inherited syndromes, 7 and 25% of CRC cases occur in individuals with at least 1 first-degree relative (FDR) with CRC. 7,8 However, CRC screening rates rarely exceed 50% among FDRs of patients with CRC. 9 Factors influencing rates of participation in CRC screening include knowledge regarding the disease and associated screening tests, and psychosocial factors.…”