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Distinctive Features of Early-Onset Colorectal Cancer

Colorectal cancer.

In adults under the age of 50, colorectal cancer (CRC) diagnoses are increasing. Researchers from the University of Texas MD Anderson Cancer Center compared CRC features in patients younger than 50 to patients older than 50 and found that there were many differences between early-onset and traditional CRC.

For this study, published in Cancer, the researchers analyzed 36,000 patients with CRC. They discovered that microsatellite instability, synchronous metastatic disease, primary tumors in the distal colon or rectum, and fewer BRAF V600 mutations were more likely to be present in patients with early-onset CRC compared with those over the age of 50 at diagnosis. Microsatellite instability indicates a problem with the DNA mismatch repair system that can lead to a mutation, and the BRAF V600 mutation affects the MAPK signaling pathway by manipulating the pathway into allowing cells to divide nonstop and resist programmed cell death.

In addition, patients under the age of 40 with CRC had fewer adenomatous polyposis coli (APC) mutations and an increased prevalence of signet ring histology compared with those over the age of 40. Upon further investigation, another difference appeared in consensus molecular subtypes (CMS): CMS1 was more common in patients under 40, and CMS3 and CMS4 were more common in patients over 40.

When the investigators considered the effect that predisposing conditions have on cancer features found in early-onset CRC versus late-onset CRC, they found differences in histological subtype. Patients younger than 50 with inflammatory bowel disease and CRC had an increased prevalence of mucinous or signet ring histology and were less likely to have APC mutations in comparison with patients younger than 50 with CRC and no predisposing conditions.

"We need to appreciate that there are unique biologic subtypes within young patients that may affect how their cancers behave and may require a personalized approach to treatment," remarked the study's senior author, Jonathan Loree, MD, Postdoctoral Fellow at the University of Texas MD Anderson Cancer Center. "Going forward, special clinical consideration should be given to, and further scientific investigations should be performed for, both very young patients with colorectal cancer and those with predisposing medical conditions."

For More Information

Willauer AN, Liu Y, Pereira AAL, et al (2019). Clinical and molecular characterization of early-onset colorectal cancer. Cancer. [Epub ahead of print] DOI:10.1002/cncr.31.994

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