A new study reveals that colorectal cancer cases among individuals under 50 have climbed by 2.9% annually between 2013 and 2022, according to the American Cancer Society. Scientists from Mass General Brigham, Dana-Farber Cancer Institute, and the Broad Institute have identified biological factors that may explain why the disease often progresses more aggressively in younger patients.
The research, published in Nature Medicine, examined 189 tumor samples from patients aged 29 to 94, including 54 cases diagnosed before age 50 and 135 cases in patients 50 or older. By employing single-nucleus RNA sequencing, the team assessed gene expression across over 850,000 cells within the tumors.
Examining Tumor Development Across Different Ages
Led by Caroline Porter of the Klarman Cell Observatory at the Broad Institute, the study utilized surgical specimens from Brigham and Women’s Hospital and samples stored in Dana-Farber’s Gastrointestinal Biobank. Additional co-senior authors included Ana C. Anderson, Kimmie Ng, and Ramnik J. Xavier.
The researchers avoided a simple age-based comparison, instead analyzing gradual biological shifts while adjusting for variables such as tumor location, disease stage, sex, and prior treatments. This method uncovered subtle differences that might have been overlooked in broader categorizations.
Tumors in younger patients exhibited unique cellular structures, featuring a higher ratio of connective and stromal cells compared to actual cancer cells. Such compositions have previously been associated with reduced chemotherapy effectiveness in multiple solid tumor types.
Unique Genetic Activity in Younger Tumors
Further validation came from analyzing 564 additional tumors and 712 stained tissue samples using computational methods. The study also detected raised activity of long non-coding RNAs—molecules that influence gene function without producing proteins—in younger patients.
Some of these RNAs appeared consistently across different cancer cell types, with many classified as “dark” RNAs, meaning their biological roles remain unclear. The data further suggested enhanced intercellular signaling in younger tumors, potentially facilitating tumor invasion and metastasis.
Ramnik J. Xavier, one of the co-senior authors, emphasized that this work advances prior research by incorporating large-scale patient data and single-cell analysis to pinpoint features exclusive to young-onset colorectal cancer.
He stated, “This work sets the stage for future mechanistic studies on how these cell programs interact with chemicals from the diet and from gut microbes to cause early-onset colorectal cancer.”
Kimmie Ng of Dana-Farber Cancer Institute, commented, “This collaborative work with Mass General Brigham researchers from the Gene Lay Institute and researchers from the Broad Institute gives us important new insight into the biology of these tumors.” The results serve as a framework for exploring distinct characteristics of early-onset colorectal cancer.
The long-term objective remains identifying new prevention, detection, and treatment approaches for young patients. Given that the American Cancer Society’s 2026 report identifies colorectal cancer as the leading cause of cancer death in individuals under 50, clarifying the disease’s biological mechanisms is vital for developing targeted interventions.