Colorectal cancer in adults under 50 often presents with distinct cellular differences and higher treatment resistance than in older patients, according to a study published in Nature Medicine.
Colorectal cancer incidence among Americans under 50 increased by 2.9% each year between 2013 and 2022, according to the American Cancer Society. The disease is now the leading cause of cancer death in this age group in the United States.
Against the backdrop of rising cases in younger adults, researchers from Ynetnews analyzed 189 tumors from colorectal cancer patients aged 29 to over 90. The project included measurements of gene activity in more than 850,000 cancer cells.
What did the cellular analysis reveal?
The goal was to look at how tumors varied across age groups. Dr. Ana Anderson, a co-senior author of the study who leads the cancer immunology program at the Gene Lay Institute at Brigham and Women’s Hospital in Boston, posed the core question in an interview with Yahoo Health.
“Is it the same colon cancer but just happening in younger people, or is there something different about it?” said Anderson.
In microsatellite-stable, or MSS, colorectal cancer, which is the most common subtype of the disease, tumors from younger patients contained a higher proportion of supporting cells relative to cancer cells. These supporting stromal cells, such as fibroblasts, can produce factors that suppress the immune response and create a shield around tumors.
“They essentially can form a shield that protects the tumor from infiltration,” Anderson told Business Insider, noting that this makes the tumors harder to treat with standard chemotherapy.
How does gene activity differ by age?
Within cancer cells from MSS tumors, researchers identified 215 genes whose expression was higher in younger patients and 44 that were more active in older patients. A substantial share of the genes more active in younger patients produce long noncoding RNA molecules, or lncRNAs.
Unlike conventional RNA that carries instructions for making proteins, these molecules do not encode proteins, although some can regulate the activity of other genes. Because lncRNAs only became linked to cancer research in the late 2000s, many remain poorly understood.
“A lot of them have just not been researched, and that’s why they’re called ‘dark RNAs’ — it’s a big mystery,” Anderson said, adding that she considers this the study’s most promising finding.
Why are younger patients diagnosed later?
Younger people also tend to be diagnosed at a more advanced stage. About three in four colorectal cancer cases among Americans under 50 are detected after the disease has spread locally or to distant organs, according to the American Cancer Society.
Distant metastases are found at diagnosis in about 27% of younger patients, compared with 21% to 23% in older age groups.
“People in their 40s don’t think they can have cancer,” said Dr. Yaron Rudnitzky, director of the Colorectal Surgery and Proctology Unit and deputy director of the Surgical Division at Meir Medical Center, part of Clalit Health Services. “Very often they have been walking around for a year with abdominal pain, bloody stools or weight loss.”
The study was conducted by scientists from Dana-Farber Cancer Institute, Mass General Brigham, and the Broad Institute. The research analyzed samples from over 50 patients under 50 out of the 189 total tumors evaluated.
Additional authors listed in the publication include Shane P. Murphy, Jules Cazaubiel, Toni M. Delorey, Liat Amir-Zilberstein, Orr Ashenberg, Liubou Klindziuk, Elizabeth Andrews, William Tan, Kosuke Matsuda, Atsushi Kondo, Satoko Ugai, Tomotaka Ugai, Shuji Ogino, Emily Finan, Jacques Deguine, Ewa Sicinska, Lauren K. Brais, and Jennifer S. Ng.
Dr. Kimmie Ng, director of Dana-Farber’s Young-Onset Colorectal Cancer Center and one of the study’s senior investigators, said that patients under the age of 50 are often diagnosed at later stages with tumors featuring more aggressive traits. Ng’s clinical interests and disclosures are managed by Dana-Farber in accordance with its conflict-of-interest policies.
Financial backing for the research was provided by the Gene Lay Institute, the Helen Gurley Brown Foundation/Dana-Farber Project P Fund, the Patrick Beauregard Fund, the Poorvu-Jaffe Fund for Young-Onset Colorectal Cancer Research, the Thau Fund, the Eigner Fund for Young-Onset Colorectal Cancer, the Klarman Cell Observatory at the Broad Institute, the National Institutes of Health, and an American Cancer Society Clinical Research Professor Award.
Kristen Vincent, a survivor who was diagnosed at age 37, commented on the research objectives, expressing hope that the work will prevent other young people and their families from enduring similar diagnoses and treatments. Vincent and medical professionals emphasize that while studies map out gradual biological shifts linked to age, individuals experiencing concerning abdominal symptoms or warning signs should seek evaluation promptly from qualified healthcare professionals.
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