“It’s been a bit of a black box,” said Ana Anderson, lead author and senior faculty member at the Gene Lay Institute of Immunology and Inflammation. at Brigham and Women’s Hospital. “We now have a research direction. We have a path to follow and hopefully find something that is really specific to this disease and that will serve as a basis for developing tailored therapies specifically for early-onset colon cancer.”
In the United States, rates of colorectal cancer in people under the age of 50 increased by almost 3% each year between 2013 and 2022, according to the American Cancer Society. Colorectal cancer is now the leading cause of cancer death in this age group.
Researchers have searched for explanations for this puzzling increase. Growing evidence links risk to diet and ultra-processed foods, among other lifestyle and environmental factors. But experts say it’s also important to understand what’s happening inside tumors and the bodies of younger patients.
In the new study published in the peer-reviewed journal Nature Medicine, scientists examined 189 tumors from people aged 20 to 90, including 54 patients diagnosed when they were younger than 50. They analyzed more than 850,000 cells. The researchers also looked for factors that changed with age, revealing subtle differences between the younger and older patients studied, said Dr. Kimmie Ng, senior author and director of the Young-Onset Colorectal Cancer Center at the Dana-Farber Cancer Institute.
The researchers observed that tumors in younger patients appeared to have a different cellular composition, namely a much higher proportion of connective and supporting cells, called stromal cells. Studies in other types of solid cancer have linked stromal cells to resistance to chemotherapy.
The study also revealed differences in how genes are expressed in tumors from younger people – a finding that experts say could lead to new therapeutic targets.
The dataset is the largest to date in colorectal cancer and includes the highest data number of young patients, Ng said.
“It gives a lot of hope,” she said. “This really serves as a guide for where we should direct our future research efforts.”
The new research gives scientists access to large amounts of detailed data, said Dr. John Paul Shen, associate professor in the department of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center.
“There are some very clear experiments that we could do in our lab or that other people would do in their labs around the world,” said Shen, who was not involved in the study. “It’s extremely valuable.”
But he and other experts noted that the data set, while vast in its cellular analysis, comes from a limited number of people. Ng said the study cohort matches what is generally known about early-onset colorectal cancer patients worldwide.
Future research could build on the study by analyzing other patient groups, said Dr. Christina Annunziata, senior vice president of extramural discovery science at the American Cancer Society.
Although the new study shows promise in helping researchers discover better ways to prevent and treat colorectal cancer in young people, experts say many advances may still be far from being realized.
According to Annunziata, having the data set is “an essential first step.”
“Research is needed to understand why people get cancer at an early stage and what we can do about it,” she said.
Allyson Chiu can be contacted at allyson.chiu@globe.com. Follow her on @_allysonchiu.
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