Genetic factors underlying colorectal cancer (CRC) development may extend beyond those patients with well-known, high-risk features, according to an article published in the Journal of Clinical Oncology.1

Referral for genetic testing occurs often among patients with colorectal cancer with high-risk features such as early age at diagnosis, personal/family history of cancer or polyps, tumor microsatellite instability, or mismatch repair deficiency. The prevalence of germline mutations in an unselected population is, however, unknown.

This study included 1058 patients who received care for CRC in a clinic-based setting. All participants underwent germline testing for mutations in 25 genes associated with inherited cancer risk.

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One or more pathogenic mutations were found in 9.9% of the study population, including 3.3% of patients who had mutations for Lynch syndrome. Seven percent of patients had non-Lynch syndrome gene mutations, including 2.2% of patients with high-penetrance genes. Identified high-penetrance genes included APC, biallelic MUTYH, BRCA1/2, PALB2, CDKN2A, and TP53.

Fifteen of the 23 patients with high-penetrance mutations lacked clinical histories that would have suggested an underlying mutation.

Another 3.6% of patients had moderate-penetrance gene mutations that included MUTYH, APC*I1307K, and CHEK2.

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“The current results demonstrate that multigene germline testing without preselection on the basis of high-risk clinical features could significantly increase opportunities for primary and secondary cancer prevention because overall, 96.2% of mutation carriers (101 of 105) had mutations in genes for which guidelines recommend specific screening and/or risk-reduction practices,” the researchers concluded. 


  1. Yurgelun MB, Kulke MH, Fuchs CS, et al. Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol. 2017 Jan 30. doi: 10.1200/JCO.2016.71.0012 [Epub ahead of print]