NCI Supports New Research into Prevention of Early-Onset Colorectal Cancer

When Chadwick Boseman, the charismatic star of “Black Panther,” died at age 43 from stage 4 colorectal cancer in 2020, it put a celebrity face on a disease once thought to occur primarily later in life. The actor’s untimely death highlighted a troubling national trend: the rising number of individuals in their early forties and even younger being diagnosed with and dying from colorectal cancer.

Early-onset cancers of the colon and rectum—defined as cancers occurring before age 50—are still considered relatively rare. But research has found that in this younger population, incidence increased 2% annually between 2008 and 2017 (nearly 10% total), while the mortality rate rose 1.3% per year during this period. The same study found that over the same period there was a reverse trend among older Americans, with colorectal cancers declining in both incidence and mortality. Individuals ages 50 to 64 had an annual .6% decline in mortality, while those over age 65 had a 3% decline in death rates each year.

Investigators attribute these trends in the older age group largely to the success of colonoscopy screening in detecting early, more treatable disease (learn more on colorectal cancer screening). But the rise in early-onset colorectal cancer in a younger population goes beyond a screening issue, they say, emphasizing the urgent need for accelerated research efforts to disrupt this concerning trend.

“Most people feel we’ve had a positive impact on colorectal cancer, which we’ve had,” said Gary Della’Zanna, D.O., a board-certified surgeon and a program official and medical officer in NCI’s Division of Cancer Prevention (DCP). “But, when we look at the age-adjusted data, the only positive is in the over-age-50 group. Data show that people born in the 1990s have twice the risk of developing colon cancer, and four times the risk of rectal cancer, as adults born in the 1950s.”

Research to Address a Growing Need

In response to this urgent need to better understand early-onset colorectal cancer, NCI recently issued a special research request called a NOSI (Notice of Special Interest) for grant applications that covers a sweeping range of issues, including: What are the risk factors and molecular biomarkers needed for early detection? What are the best screening tools for finding cancer in a younger population? And how can clinicians develop effective intervention strategies that prevent the early onset of colorectal disease?

In the past, researchers have found it difficult to find participants willing to take part in studies on the risk colorectal cancers can pose in a younger age group, citing bias, ignorance, or both, Dr. Della’Zanna said. Physicians and patients alike, he said, might ignore the red-flag symptoms that may seem embarrassing and signal the presence of early disease in older adults, including changes in bowel habits, abdominal pain, rectal bleeding, and blood in the stool.

However, “one of the most common reasons for this may be that younger people do not receive recommendations to undergo diagnostic workups,” when they have these symptoms, said Asad Umar, D.V.M., Ph.D., a senior advisor to the director for translational research in DCP.  As a result, physicians typically discover these cancers in advanced stages when survival is poor, he explained.

Through the newly proposed grant funding, NCI hopes to alter these dismal prospects in younger colorectal cancer patients by increasing public awareness and stimulating research into the molecular and biological underpinnings distinguishing early-onset colorectal cancers from late-onset disease.

Observational studies have identified several shared general risk factors common to many cancers, such as diabetes, smoking history, and poor dietary habits, researchers say. But specific differences also exist that distinguish colorectal cancer. For example, scientists have characterized differences in where colon and rectal tumors first arise, which may have a bearing on how well patients do, and they have located regional pockets in the country where early-onset colorectal cancers occur at the highest rates. In addition, they’ve identified racial and socioeconomic factors that may further understanding and have found that at least 30% of early-onset colorectal cancers have a known hereditary link.

“By definition, familial cancers such as Lynch syndrome tend to have earlier onset of these cancers under age 45,” Dr. Umar said. “It’s not surprising we find higher numbers in this population. But it doesn’t explain why the rates keep going up, as the prevalence of hereditary colorectal cancers has not changed.”

Researchers also know environmental factors may play a role, as normal cells progress to malignancy. Several possible triggers now under study, Dr. Umar said, include increasing levels of obesity and an overuse of antibiotics, especially during pregnancy. Investigators also have begun tracking changes in the vast array of gut bacteria found in the microbiota for clues behind the incremental rise in colorectal cancers since the mid-1980s in people under age 50.

Three major health care organizations have taken note of these trends. In 2018, the American Cancer Society became the first to lower its recommended screening guidelines for colonoscopy from age 50 to age 45 in average-risk individuals. More recently, both the American College of Gastroenterology and the U.S. Preventive Services Task Force have followed suit, calling for a similar lower age to begin these tests.

Eventually, it seems probable that screening approaches will need tailoring to a younger population as part of future research efforts, according to Dr. Della’Zanna.

“All of our approved screening, so far, has been validated only in an older population,” he said. “So, we will need to look at the benefits and risks of other screening strategies in a younger age group.”

Therefore, NCI researchers hope the new research request will lead to applications for studies that will establish evidence that can contribute to screening guidelines for early-onset colorectal cancer, as well as studies investigating the molecular or genetic drivers that account for racial and ethnic disparities in early-onset colorectal cancer and the molecular signatures of early-life influences or exposures and social determinants of health that explain this rising trend over the last several decades.

The NOSI on Research on the Etiology, Early Detection, Screening and Prevention of Early-Onset Colorectal Cancer was issued in January 2023.

Learn more from the NCI Cancer Currents blog.