Colorectal cancer rates ticked up in 2023 following years of decline. A new single-cell atlas published in Nature Medicine reveals that tumors in patients under 50 possess distinct cellular compositions and genetic features that may explain why early-onset disease often behaves more aggressively.
Surveillance data show that the disease climbed slightly in 2023. A massive genetic mapping effort involving 189 tumors has laid bare the biological differences separating early-onset cases from those diagnosed in older adults.
The findings offer a close look at a disease that has increasingly troubled physicians, particularly as incidence rates rise among younger adults while falling in older populations.
SEER Data Shows a Modest Increase in 2023
While the rate of colorectal cancer in U.S. adults dropped substantially from 2000 to 2022, it ticked up in 2023, according to an assessment of nationwide data published in a Public Health Alerts report.
The data stem from the Surveillance, Epidemiology, and End Results (SEER) Program, specifically SEER 21, which covers 21 geographic cancer registry areas representing 45.8% of the U.S. population. The age-adjusted incidence rate was 55.2 per 100,000 in 2000, fell to 36.7 per 100,000 in 2022, and rose to 38.3 per 100,000 in 2023. The report notes that although modest, this apparent increase was the first since the inception of SEER 21 in 2000. Researchers speculate this reflects a birth cohort effect, where adults born since the 1960s face increasing risk as they enter middle age.
| Year | SEER 21 Age-Adjusted Incidence Rate (per 100,000) |
|---|---|
| 2000 | 55.2 |
| 2022 | 36.7 |
| 2023 | 38.3 |
Single-Cell Analysis Uncovers Unique Tumors
To understand why early-onset colorectal cancer tends to be more aggressive, researchers analyzed 189 colorectal tumors—including 54 from patients under 50 and 135 from patients over 50—mapping gene activity across more than 850,000 cells.
The study, published in Nature Medicine, represents the largest single-cell atlas of its kind. Co-senior author Ana Anderson noted that the comprehensive approach aimed to resolve a fundamental question.
Is it the same colon cancer but just happening in younger people, or is there something different about it?
Ana Anderson, Gene Lay Institute at Brigham and Women’s Hospital, via Business Insider
The analysis revealed that tumors in younger patients feature a higher proportion of supporting and connecting cells, known as stromal cells, compared to malignant cancer cells. Researchers also identified gene activity suggesting enhanced cell-to-cell communication, which may help cancer cells migrate and invade nearby tissue more easily.
Dark RNAs and Uncharted Biology in Early-Onset Tumors
Among the study’s discoveries was an increased expression of long non-coding RNAs—molecules that regulate genes without making proteins. Many of these are poorly understood sequences known as “dark RNAs” because they have not been thoroughly researched since becoming linked to cancer studies in the late 2000s.
A lot of them have just not been researched, and that’s why they’re called ‘dark RNAs’ — it’s a big mystery.
Ana Anderson, Gene Lay Institute at Brigham and Women’s Hospital, via Business Insider
These molecular differences point toward potential therapeutic targets, though experts caution that clinical breakthroughs will take time. Kimmie Ng, director of the Young-Onset Colorectal Cancer Center at the Dana-Farber Cancer Institute, emphasized the value of the new roadmap.
Our study lays the foundation for future functional studies to characterize the mechanism of action underlying our findings, including the increased proportion of stromal cells, the differentially expressed genes, and the increased cell-cell communication.
Kimmie Ng, Dana-Farber Cancer Institute, via Inside Precision Medicine
Warning Signs for Younger Populations
Colorectal cancer now stands as the leading cause of cancer death for individuals under 50 in the U.S. Clinicians emphasize vigilance regarding symptoms.
While routine screening recommendations have been adjusted to begin at age 45, younger individuals experiencing persistent symptoms often face diagnostic delays.
Dr. Sandra Kavalukas, a colorectal surgeon at the University of Louisville School of Medicine, highlighted that rectal bleeding serves as a critical red flag in younger cohorts who are 8.5 times more likely to have colorectal cancer when presenting with a bleeding complaint. Sandra Kavalukas is a colorectal surgeon at the University of Louisville.
While researchers continue investigating lifestyle factors, environmental exposures, and potential microbiome disruptions, exact environmental triggers remain unproven.