Results from a retrospective study of a large number of patients with colorectal cancer (CRC) grouped according to age identified a number of clinical characteristics and molecular features more common in patients with early-onset disease (ie, disease diagnosed in patients aged <50 years). The findings from this study were published online in Cancer.1
While most cases of CRC occur in older individuals, the incidence of this disease is increasing for adults aged younger than 50 years. In response to this trend, the American Cancer Society has recently recommended that CRC screening should start at age 45 years for adults at average risk of the disease.2
In addition, recent advancements in the molecular categorization of CRC have included the identification of 4 consensus molecular subtypes (CMS) of CRC: CMS1 (“hypermutated, microsatellite unstable, strong immune activation”); CMS2 (“epithelial, chromosomally unstable, marked WNT and MYC signaling activation”); CMS3 (“epithelial, evident metabolic dysregulation”); and CMS4 (“prominent transforming growth factor β activation, stromal invasion, and angiogenesis”).3
This study used data for more than 36,000 unique patients derived from 4 separate cohorts: 1877 patients with metastatic CRC with mutational and baseline clinicopathologic data from MD Anderson Cancer Center (MDACC); 32,507 patients with stage I to stage IV disease and baseline clinicopathologic data included in the tumor registry from MDACC; 1868 patients with mostly stage IV disease with mutational and limited clinicopathologic data included in the Genomics Evidence Neoplasia Information Exchange (GENIE) cohort from the American Association for Cancer Research (AACR); and 626 patients with stage I to stage IV disease included in the CMS cohort with RNA expression data allowing for categorization of disease by CMS, and limited clinicopathologic data.
Key findings from this study showed that, compared with those aged 50 years or older, patients with early-onset disease were more likely to have the following disease characteristics:
- Microsatellite instability-high (P =.038)
- Synchronous metastatic disease (P =.009)
- Left-sided or rectal tumors (combined P <.0001)
- A lower frequency of BRAF V600 mutations (P <.001)
Furthermore, patients aged 18 to 29 years were more likely to have disease characterized by signet ring histology (P <.001) and less likely to have disease characterized by adenomatous polyposis coli (APC) mutations (P =.015) when compared with other patients aged younger than 50 years.
The most common CMS subtype in patients 40 years of age was CMS1, with CMS3 and CMS4 found to be uncommon in this age group (P =.003). Interestingly, the frequency of disease categorized as CMS2 was relatively similar across all 6 age groups studied (ie, 18-29 years; 30-39 years; 40-49 years; 50-59 years; 60-69 years; ≥70 years).
Compared with patients aged younger than 50 years without predisposing conditions, those with early-onset CRC and inflammatory bowel disease had disease that was significantly more likely to be characterized by mucinous histology (P =.0004) and significantly less likely to have APC mutations (P =.019).
“In conclusion, early-onset CRC has distinct clinical and molecular features, and it may be more appropriate to consider age as a continuum when one is evaluating CRC,” the study authors wrote.
- Willauer AN, Liu Y, Pereira AAL, et al. Clinical and molecular characterization of early-onset colorectal cancer. Cancer [published online on March 11, 2019]. doi: 10.1002/cncr.31994
- American Cancer Society Guideline for Colorectal Cancer Screening. https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/acs-recommendations.html. Accessed March 11, 2019.
- Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015; 21: 1350–1356.