Study shows early-onset colorectal cancers have distinct features

Through in-depth retrospective analysis of data from more than 36,000 patients, a new study led by researchers at The University of Texas MD Anderson Cancer Center found that early-onset colorectal cancer (CRC) has distinct clinical and molecular features compared to those diagnosed later in life. Their findings were published recently in the journal CANCER.

The researchers discovered that patients with early-onset CRC, those diagnosed before age 50, were more likely to have metastatic disease at diagnosis, microsatellite instability and tumors in the left-side of the colon and rectum when compared to late-onset disease. On the other hand, those with early-onset CRC were less likely to have BRAF V600 mutations so common in patients over 50 and targetable with drugs.

“It’s clear from our research that early-onset colorectal cancer has unique features compared to other colorectal cancers,” said Scott Kopetz, M.D., Ph.D., associate professor of Gastrointestinal Medical Oncology and corresponding author on the study. “We don’t yet fully understand the cause of early-onset disease, but we now understand that it is a distinct disease that may one day necessitate different screening or treatment methods.”

Colorectal cancer is the third-most common cancer type in the U.S., and the second-leading cause of cancer deaths. It has traditionally been a disease of older adults, with the majority of cancers diagnosed in those over 50. Fortunately, the incidence of these cancers has been decreasing thanks to improved prevention and early detection efforts. However, the incidence of CRC among adolescents and young adults under 50 has increased by as much as 3 percent annually in recent years, and many of those are not hereditary.

In an effort to better understand early-onset disease and lay a foundation for determining its root causes, the research team performed a retrospective analysis of more than 36,000 patients from four cohorts. The research was led by the Colorectal Cancer Moon Shot™ team, who are driven to make transformative advances in prevention, screening and treatment approaches for patients with CRC. Their effort is part of MD Anderson’s Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients’ lives.

“The Colorectal Cancer Moon Shot is a key driver of our collaborative work to bring impactful new therapies and prevention approaches to the clinic,” said Kopetz. “The support of the Moon Shots program and its unique infrastructure has enabled research, such as this, that propel us toward a better understanding of the disease while keeping us aligned with our singular goal – impact for our patients.”

The detailed analysis revealed that patients younger than 50 had a significantly higher prevalence of tumors located on the distal, or left-side, portion of the colon or in the rectum. The location of tumors in these younger individuals may have screening implications, explained Kopetz, as different techniques may prove more useful to screen in these locations. Additionally, these patients were more likely to have metastases at diagnoses.

In addition, the genetic landscape was different when comparing early-onset and late-onset disease. Patients with early-onset colorectal cancer were more likely to have high microsatellite instability and mutations in the CTNNB1 gene, but less likely to have BRAF V600 mutations – a common driver of colorectal cancers. Very young patients (18-29) were less likely to have mutations in the APC gene.

Further, younger patients appeared to have a different prevalence of cancers with certain consensus molecular subtypes (CMS), a classification system pioneered by the Moon Shot team. The prevalence of these subtypes differed significantly by age group, with CMS1 being most common in patients younger than 40, and CMS3 and 4 relatively uncommon in this age group.

Taken together, these different characteristics may suggest alternative therapeutic approaches that may be more effective in treating early-onset, CRC, though prospective clinical studies will be needed to confirm that hypothesis, said Kopetz.