From the Journals

Distinct features found in young-onset CRC



Young-onset colorectal cancer (CRC) has distinct clinical and molecular features, compared with disease diagnosed later in life, according to investigators who conducted a review that included more than 36,000 patients.

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CRC patients younger than 50 years of age were more likely to have distal primary tumors, synchronous metastatic disease, and microsatellite instability (MSI) than were older patients, investigators said. Conversely, those younger patients were less likely to have BRAF V600 mutations than were patients 50 years old and older, the investigators reported in the journal Cancer.

Very young patients were more likely to have signet ring histology and less likely to have adenomatous polyposis coli (APC) mutations, according to senior study author Jonathan M. Loree, MD, and his coinvestigators at The University of Texas MD Anderson Cancer Center, Houston.

“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,” Dr. Loree said in a press statement. “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.”

The incidence of young-onset CRC has increased 1%-3% annually in recent years, Dr. Loree and colleagues wrote in their report.

Although smaller studies have characterized molecular features of CRC in younger patients, there has so far been no comprehensive molecular characterization of these patients, they added. Accordingly, the investigators conducted a retrospective analysis that included more than 36,000 patients in four different patient cohorts.

Patients under 50 years more likely had synchronous metastases (P = .009), more likely had primary tumors in the distal colon and rectum (P less than .0001), and were more likely to be MSI-high (P = .038), compared with their older counterparts, Dr. Loree and coauthors reported.

BRAF V600 mutations were infrequent in patients under 30 years of age, at a prevalence of 4% or less, increasing to a high of 13% in patients aged 70 years or older (P less than 0.001), investigators also reported.

Very young patients, or those aged 18-29 years, had a higher prevalence of signet ring histology, compared with the other age groups (P = .0003), and they had a nearly fivefold increased odds of signet ring histology compared with patients in the 30-49 year age range, investigators wrote.

There were also considerably fewer APC mutations in the patients younger than 30 years, compared with older patients in the young-onset CRC group, with an odds ratio of 0.56 (95% confidence interval, 0.35-0.90; P = .015).

Hispanic patients were significantly overrepresented in the under-30-years age group (P = .0015), according to the report.

For patients under 50 years who also had inflammatory bowel disease, odds of mucinous or signet ring histology were higher (OR, 5.54; 95% CI, 2.24-13.74; P = .0004), and odds of APC mutations were lower (OR, 0.24; 95% CI, 0.07-0.75; P = .019), compared with younger patients with no such predisposing conditions.

“These notable differences in very young patients with CRC and those with predisposing conditions highlight that early-onset CRC has unique subsets within the population of patients younger than 50 years,” Dr. Loree and coauthors concluded.

Support to investigators in the study came from the National Cancer Institute, National Institutes of Health, and the MD Anderson Colorectal Cancer Moon Shot Program. One coinvestigator reported disclosures related to Roche, Genentech, EMD Serono, Merck, Karyopharm, Amal, Navire, Symphogen, Holystone, Biocartis, Amgen, and Novartis.

SOURCE: Willauer AN et al. Cancer. 2019 Mar 11. doi: 10.1002/cncr.31994

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