Hereditary colorectal cancer syndromes

Abstract

SUMMARY Colorectal cancer (CRC) is one of the most common malignancies and the second-leading cause of cancer death in both sexes in developed countries. Over the last 25 years, highly penetrant monogenic germline mutations that predispose to CRC and other digestive tumors have been identified, accounting for up to 5% of all CRC cases. Identification and characterization of these disorders have allowed modification of their natural history, with a substantial decrease in morbidity and mortality among high-risk patients. Recognizing hereditary CRC has also impacted predictive genetic testing and personalized medicine based on genomic information. This review summarizes the current knowledge on hereditary CRC regarding pathogenesis, clinical features, diagnostic evaluation and management recommendations.

Financial & competing interests disclosure

This work was supported by grants from the Instituto de Salud Carlos III (PI10/00384) ‘Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, Una manera de hacer Europa‘, and a grant from the Spanish Gastroenterology Association (Gonzalo Miño). CIBERehd is funded by the Instituto de Salud Carlos III. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

^†Lynch syndrome-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain (usually glioblastoma as seen in Turcot syndrome), sebaceous gland adenomas and keratoacanthomas in Muir–Torre syndrome, and carcinoma of the small bowel.

^‡Presence of tumor-infiltrating lymphocytes, Crohn‘s-like lymphocytic reaction, mucinous/signet-ring differentiation or medullary growth pattern.

^§There was no consensus among the workshop participants to include the age criteria; participants voted to keep less than 60 years of age in the guidelines.

MSI-H: Microsatellite instability high.

Additional information

Funding

This work was supported by grants from the Instituto de Salud Carlos III (PI10/00384) ‘Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, Una manera de hacer Europa‘, and a grant from the Spanish Gastroenterology Association (Gonzalo Miño). CIBERehd is funded by the Instituto de Salud Carlos III. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.