March 11, 2019
2 min read

Early-onset colorectal cancer clinically, molecularly distinct from late-onset disease

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Early-onset colorectal cancer appears to have different clinical and genetic characteristics than colorectal cancer diagnosed later in life, according to results of a retrospective study published in Cancer.

“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,” Jonathan Loree, MD, BMSc, FRCPC, who served as a gastrointestinal medical oncology clinical research fellow at The University of Texas MD Anderson Cancer Center during the conduct of the study, and is now assistant professor at The University of British Columbia and medical oncologist at BC Cancer, said in a press release. “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.”

Colorectal cancer is among the top three most widespread and deadly cancers for men and women, with incidence rising 1% to 3% annually in those aged younger than 50 years, according to study background. However, preventive screening has led to a decrease in incidence and mortality among individuals aged older than 50 years.

Researchers analyzed baseline characteristics according to age of onset in three separate cohorts of patients with colorectal cancer. The analyzed a fourth cohort to describe the impact age had on the prevalence of consensus molecular subtypes.

The review included more than 36,000 patients.

Results showed that patients diagnosed before age 50 years were more likely to have microsatellite instability (P = .038), synchronous metastatic disease (P = .009), primary tumors in the distal colon or rectum (P < .0001), and fewer BRAF V600 mutations (P < .001) than patients diagnosed at age 50 years or older.

Patients diagnosed when aged 18 to 29 years had fewer adenomatous polyposis coli mutations (OR = 0.56; 95% CI, 0.35-0.9) and an increased prevalence of signet ring histology (OR = 4.89: 95% CI, 3.23-7.39) than other patients aged younger than 50 years.

Among patients younger than age 40 years, CMS1 was the most common subtype and CMS3 and CMS4 appeared uncommon (P = .003). CMS2 incidence was stable across all age groups.

Patients aged younger than 50 years who had inflammatory bowel disease appeared more likely to have mucinous or signet ring histology (OR = 5.54; 95% CI, 2.24-13.74) and less likely to have adenomatous polyposis coli mutations (OR = 0.24; 95% CI, 0.07-0.75) than other patients aged younger than 50 years with no predisposing conditions.


Data on certain clinical or molecular variables — such as predisposing conditions — was missing from three of the four cohorts, which served as a limitation to the study.

“This study has identified unique clinical and molecular features of early-onset colorectal cancer from more than 36,000 patients and has demonstrated a novel continuum of changes suggesting that not all patients younger than 50 years are homogeneous, but rather there are additional unique molecular and clinicopathologic features in patients younger than 30 years and in patients with predisposing conditions,” Loree and colleagues wrote. “The etiology of the high rate of CMS1 in patients younger than 40 years deserves further exploration.” – by John DeRosier

Disclosures: Loree reports no relevant financial disclosures. One author reports personal fees from Amal Therapeutics, Amgen, Biocartis, EMD Serono, Genentech, Holystone, Karyopharm Therapeutics, Merck, Navire Pharma, Novartis, Roche and Symphogen outside the submitted work.