Clinical and molecular characterization of early-onset colorectal cancer

Background: Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated clinical and molecular features to identify those features unique to early-onset CRC that differentiate these patients from patients 50 years old or older. Methods: Baseline characteristics were evaluated according to the CRC onset age with 3 independent cohorts. A fourth cohort was used to describe the impact of age on the consensus molecular subtype (CMS) prevalence. Results: This retrospective review of more than 36,000 patients with CRC showed that early-onset patients 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) in comparison with patients 50 years old or older. Patients aged 18 to 29 years had fewer adenomatous polyposis coli (APC) mutations (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.35-0.90; P =.015) and an increased prevalence of signet ring histology (OR, 4.89; 95% CI, 3.23-7.39; P <.0001) in comparison with other patients younger than 50 years. In patients younger than 40 years, CMS1 was the most common subtype, whereas CMS3 and CMS4 were uncommon (P =.003). CMS2 was relatively stable across age groups. Early-onset patients with inflammatory bowel disease were more likely to have mucinous or signet ring histology (OR, 5.54; 95% CI, 2.24-13.74; P =.0004) and less likely to have APC mutations (OR, 0.24; 95% CI, 0.07-0.75; P =.019) in comparison with early-onset patients without predisposing conditions. Conclusions: Early-onset CRC is not only distinct from traditional CRC: special consideration should be given to and further investigations should be performed for both very young patients with CRC (18-29 years) and those with predisposing conditions. The etiology of the high rate of CMS1 in patients younger than 40 years deserves further exploration.