Colorectal cancer is often thought to affect older people, but one in five cases diagnosed today occurs in people younger than age 55, compared to one in 10 cases in 1995, according to a recent study published by the American Cancer Society.
There’s no clear explanation for this trend, but a new paper just published in Science suggests a number of possible reasons, including environmental and genetic factors. Low screening rates and misdiagnosis in people who don’t suspect cancer likely play a role as well.
“We're coming to a point where we shouldn't consider colorectal cancer a disease of only older adults,” said Andrew Chan, a professor of medicine at Harvard Medical School and vice chair of gastroenterology at Massachusetts General Hospital.
The findings also revealed an increase in diagnoses of advanced disease, which is particularly concerning because colonoscopies are “a great tool for prevention and early detection of colorectal cancer in terms of screening that can actually detect and remove precancerous lesions,” said lead author Rebecca Siegel, senior scientific director of cancer surveillance research at the American Cancer Society. Survival rates are 90 percent if detected early enough.
The rising rates in younger adults led the U.S. Preventive Services Task Force to change its recommendation in May 2021 to begin screenings at age 45 instead of 50, but those with risk factors may need to start even earlier, said Siegel, who noted that nearly a third of colorectal cancers are associated with a family history of the disease.
“Until we see these trends start to reverse, we're going to have to continue to consider what appropriate strategies we need to take to really stem this increase in early onset disease,” Chan said.
Identifying colorectal risk factors
Genetic risk scores may be helpful for identifying those who may be more likely to develop colorectal cancer at an early age but could be more effective if they took interaction with environmental factors into account, suggested Marios Giannakis, an oncologist at Dana-Farber Cancer Institute who coauthored the Science paper. The question is which environmental factors? Finding out requires the kind of long-term studies of large populations that are expensive and difficult to conduct, especially since they would be most useful if they included stool, blood, and tissue samples collected over time.
Lifestyle factors seem an easy culprit for early onset disease at first, but the reality is more complicated. Excess body weight increases the risk of colorectal cancer, Siegel said, but only about 5 percent of colorectal cancers are attributed to excess body weight. Excess weight is also predominantly linked to tumors on the right side of the colon, not the left colon, which is where the cancer society found that the increases are occurring.
Excess weight is also a bigger risk factor for men than women, yet the trend in younger adults is similar for all people.
“Diet, obesity, and physical inactivity may be driving some of this increase, but it's not the complete story,” Chan said. “There are other contributors that remain to be uncovered, and I think it's those factors on which we need to really focus our attention because they're going to be things that may potentially have a greater impact in reducing incidence.”
Giannakis’s paper notes that higher consumption of sugar-sweetened beverages, as well as red and processed meats are possible factors. Others include “antibiotics, more ubiquitous environmental toxins, and higher rates of Cesarean sections and other surgical procedures.”
What all those factors have in common is an effect on the microbiome, the population of bacteria and other microorganisms that populate the human digestive system. Mark A. Lewis, director of gastrointestinal oncology at Intermountain Health in Utah, said early onset disease is at least “partly explained by antibiotic usage in childhood and young adulthood, as shown most convincingly,” in 2019 study from the United Kingdom.
Don’t dismiss troublesome symptoms
It’s challenging to tease out how much increased mortality is due to greater risk factors versus low screening rates, particularly in rural or low-income areas, but it’s likely both, said Rishi Naik, an assistant professor of medicine in gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center.
Screening gaps are evident in the fact that 27 percent of younger adults are diagnosed with advanced disease compared to 20 percent of older adults. Survival rates are similar across ages despite younger patients typically receiving more aggressive treatment and having fewer other conditions.
“We fear this may also indicate a more aggressive biology for reasons that we need to understand,” Giannakis said, but it’s still not clear whether disease in younger people is more aggressive or just getting caught too late or both. Siegel’s paper noted that symptomatic patients under age 50 took 40 percent longer to receive a diagnosis compared to older patients.
“It is important for patients and providers to aggressively investigate concerning symptoms and signs, such as rectal bleeding and unexplained iron deficiency, to ensure that unsuspected colorectal cancer is not the cause, regardless of age,” said Reid Ness, an associate professor of medicine in gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center.
The most common symptoms for colorectal cancer in younger patients are abdominal pain; unexplained weight loss; changes in the frequency, size or appearance of stools; and rectal bleeding, which occurs in 46 percent of early-onset cases compared to 26 percent of cases in adults over age 50.
“There is a tendency for young people to assume that they're young and healthy, and if they do have some symptoms, that it's something transient or not concerning,” Chan said. Siegel also noted the importance of fighting stigma since people may not feel comfortable discussing rectal symptoms. But following up means ensuring doctors take symptoms seriously too.
“Sometimes the more unfortunate stories are patients told they just have a hemorrhoid, and then a couple months later, they’ve got metastatic colon cancer,” Naik said. “If they’re symptomatic, they need a colonoscopy and not just a stool-based test.”
Health disparities reveal need for more screening
Like the trend toward more cases in younger ages, racial and ethnic disparities in colorectal cancer rates and deaths likely result from a combination of greater risk factors and lower screening rates and health-care access.
Siegel highlighted that Alaskan Natives have the highest rates of colorectal cancer in the world. Cases in this population are more than double those among white individuals, and deaths are nearly four times higher in the Alaskan Native population—the only racial or ethnic group in which overall cases are not declining. In fact, cases are increasing by 2 percent each year and remain the most diagnosed cancer in this group.
Possible contributing risk factors for cases in this population include vitamin D deficiency from less sun exposure, smoking, obesity, and a diet high in smoked fish and low in fiber, fruits, and vegetables, according to Siegel’s study.
The disparity between cases and deaths is more striking in Black Americans, whose cases are 21 percent higher than in white Americans but whose mortality is 44 percent higher. Three-year survival rates for metastatic rectal cancer are 30 percent for patients diagnosed between 2016-2018—up from 25 percent a decade earlier—but Black patients’ three-year survival rates have plateaued at 22 percent, likely due to lower access to improved treatments, Siegel and her coauthors write.
Geographic disparities are similarly driven at least partly by higher rates of smoking and excess body weight, as well as lower income and poorer health-care access, Siegel said. Both cases and mortality are lowest in the West and highest in Appalachia and parts of the South and Midwest.
“If you look at a map of county-level poverty and county-level colorectal cancer mortality, they're strikingly similar,” Siegel said. Excess weight and poorer diets are more common with lower incomes, especially since processed foods are cheaper and less likely to spoil than fresh foods, Siegel said.
Another contributing factor to disparities is inadequate information about screening options besides colonoscopy, said Naik. Colonoscopies require going to centers, which are sparser in Alaska and rural areas. Colonoscopies also typically involve anesthesia, which means the patient must take off work and have someone else, who may also need time off work, drive them home—all of which is more difficult for people with low incomes.
“Though colonoscopies are a gold standard for screening for colon cancer, it's not the only modality,” Naik said. “We also have stool-based testing, which can be done at the comfort of your home.” Although providers play a critical role in encouraging screening, “really health-care systems have to do a better job of engaging communities on a programmatic level,” he said.
Ness takes that idea even further. “The greatest source of disparity in colorectal cancer incidence and mortality remains the low screening rates among uninsured and low-income individuals,” he said. “Until we in the United States become committed to the concept and practice of universally available basic health care, including colorectal cancer screening, we will continue to see disparities in health outcomes.”