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Genetics of Colorectal Cancer (PDQ®)

Health Professional Version
Last Modified: 07/11/2014

Changes to This Summary (07/11/2014)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.


Added National Comprehensive Cancer Network (NCCN) as reference 73.

Major Genetic Syndromes

Revised Table 4, Absolute Risks of Colorectal Cancer (CRC) for Mutation Carriers in Hereditary CRC Syndromes, to add a footnote to state that cancer risk estimates for familial adenomatous polyposis (FAP) predate the widespread use of surveillance and prophylactic surgery.

Revised Table 7, Recommended Screening Intervals by Spigelman Stage, to state that NCCN now recommends expert endoscopic surveillance every 3 to 6 months for Spigelman stage IV CRC (cited NCCN as reference 92).

Revised text to state that colon adenomas will develop in nearly 100% of persons who are APC gene mutation–positive; risk-reducing surgery comprises the standard of care to prevent colon cancer after polyps have appeared and are too numerous or histologically advanced to monitor safely using endoscopic resection.

Added Table 9, Clinical Practice Guidelines for Colon Surveillance of Attenuated Familial Adenomatous Polyposis.

Added Table 10, Clinical Practice Guidelines for Colon Surveillance of Biallelic MYH-Associated Polyposis.

Revised text to state that in Caucasian populations of northern European descent, two major variants, Y179C and G396D, account for 70% of biallelic mutations in MYH-associated polyposis patients, and 90% of these patients carry at least one of these mutations.

Added text to state that the mismatch repair genes MSH2, MLH1, MSH6, and PMS2 were formerly referred to as hMSH2, hMLH1, hMSH6, and hPMS2, respectively, with the “h” designating them as human homologs; for simplicity, the “h” was dropped.

Added text to state that some refer to familial colorectal type X as “Lynch-like syndrome.” The term “Lynch-like” has also been used in cases with microsatellite instability (MSI)-high tumors and presumed underlying mismatch repair germline mutation, but in which no such mutation is detected.

Revised text to state that Lynch syndrome (LS) accounts for about 1% to 3% of all CRCs. Also revised text to state that the average age at diagnosis of CRC in mutation-positive families was reported to be 61 years, suggesting ascertainment bias in early reports.

Revised text to state that the most common extracolonic malignancy in LS is endometrial adenocarcinoma, which affects at least one female member in about 50% of LS pedigrees.

The Historical criteria for defining LS families section was extensively revised.

Revised text to state that NCCN 2014 guidelines support immunohistochemistry (IHC) testing of all CRCs diagnosed in patients younger than 70 years if tumor is available and in patients 70 years or older if they meet Bethesda guidelines.

Added text about a study that compared four strategies for tumor testing for the diagnosis of LS; the strategy of tumor testing all individuals diagnosed with CRC aged 70 years or younger and testing older individuals who met one of the revised Bethesda guidelines yielded a sensitivity of 95.1%, a specificity of 95.5%, and a diagnostic yield of 2.1%.

Revised Table 11, Practice Guidelines for Diagnosis and Colon Surveillance of LS, to refer the reader to the NCCN 2014 guidelines for more information about surveillance in families in whom a tumor has shown informative IHC and MSI but no germline is mutation found.

Revised Table 14, Published Recommendations for Diagnosis and Surveillance of Juvenile Polyposis Syndrome (JPS), to state that NCCN recommends SMAD4 and BMPR1A genetic testing for the diagnosis of JPS.

This summary is written and maintained by the PDQ Cancer Genetics Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.