Colorectal cancer is often thought to affect older people, according to a recent study published by the American Cancer Society, but one in five cases diagnosed today occurs in people under the age of 55, compared with one in 10 cases in 1995.
There is no clear explanation for this trend, but a new paper that has just been published does Science suggests a number of possible reasons, including environmental and genetic factors. Low screening rates and misdiagnosis in people who don’t suspect cancer also likely play a role.
“We’re getting to a point where we shouldn’t just think of colorectal cancer as a disease of older adults,” said Andrew Chan, professor of medicine at Harvard Medical School and vice chair of gastroenterology at Massachusetts General Hospital.
The results also showed an increase in diagnoses of advanced disease, which is particularly worrying given that 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 as high as 90 percent if caught early enough.
Rising rates among younger adults prompted the U.S. Preventive Services Task Force to change its recommendation in May 2021 to start screenings at age 45 instead of 50, but those with risk factors may need to start even earlier, said Siegel, who noted that almost a third of colorectal cancer cases are linked to a family history of the disease.
“Until we see these trends reverse, we must continue to consider what appropriate strategies we must adopt to truly contain this increase in early-onset disease,” Chan said.
Identification of colorectal risk factors
Genetic risk scores may be helpful in identifying those who are more likely to develop colorectal cancer early, but could be more effective if they take into account interaction with environmental factors, suggested Marios Giannakis, an oncologist at the Dana-Farber Cancer Institute, who co-author of Science Paper. The question is, what environmental factors? Finding this out will require expensive and difficult-to-perform long-term studies in large populations, which would be most useful if they included stool, blood and tissue samples collected over time.
Lifestyle factors may at first appear to be an easy cause of early onset disease, but the reality is more complicated. Excessive body weight increases the risk of colon cancer, Siegel said, but only about 5 percent of colon cancer cases are attributed to obesity. Obesity is also predominantly associated with tumors on the right side of the colon, not the left colon where the cancer society has determined the increases occur.
Obesity is also a greater risk factor for men than for women, but the trend in younger adults is similar for all people.
“Diet, obesity and physical inactivity could be driving some of this increase, but it’s not the whole story,” Chan said. “There are other factors that have yet to be uncovered and I think it’s those factors that we really need to focus our attention on as they will potentially have a greater impact in reducing incidence.”
Giannakis’ paper notes that higher consumption of sugar-sweetened beverages and red and processed meat are possible factors. Others include “antibiotics, more pervasive environmental toxins, and higher rates of cesarean sections and other surgical procedures.”
What all of these factors have in common is an effect on the microbiome, the population of bacteria and other microorganisms that inhabit the human digestive system. Mark A. Lewis, director of gastrointestinal oncology at Intermountain Health in Utah, said in a 2019 UK study that the early onset of disease is at least “in part due to the use of antibiotics in childhood and young adulthood it is explained how it is shown most convincingly”.
Don’t ignore bothersome symptoms
It’s difficult to figure out how much the 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 reflected 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, although younger patients typically receive more aggressive treatment and have fewer other disorders.
“We’re concerned that this could also suggest a more aggressive biology for reasons we need to understand,” Giannakis said, but it’s still not clear whether the disease is more aggressive in younger people or simply caught too late, or both . Siegel’s article found that symptomatic patients under the age of 50 took 40 percent longer to receive a diagnosis compared to older patients.
“It is important that patients and healthcare professionals aggressively look for symptoms and signs such as rectal bleeding and unexplained iron deficiency to ensure that regardless of age, unexpected colorectal cancer is not the cause,” said Reid Ness, associate professor of medicine in gastroenterology, hepatology and Nutrition at Vanderbilt University Medical Center.
The most common symptoms of 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 with 26 percent of cases in adults over 50 years of age.
“Young people tend to assume that they’re young and healthy, and if they have some symptoms, that it’s something temporary or nothing to worry about,” Chan said. Siegel also pointed out the importance of fighting stigma, as people may not feel comfortable talking about rectal symptoms. But follow-up care means making sure doctors take the symptoms seriously.
“Sometimes the more unfortunate stories are that patients are told they just have one hemorrhoid, and then a few months later, they have metastatic colon cancer,” Naik said. “If they’re symptomatic, they need a colonoscopy and not just a stool-based test.”
Health disparities show that more screening is needed
Like the trend toward more cases in younger age groups, racial and ethnic disparities in colorectal cancer rates and deaths likely result from a combination of greater risk factors and lower rates of screening and access to health care.
Siegel pointed out that Alaska Natives have the highest rate of colon cancer in the world. Cases in this population are more than double those of whites, and deaths are nearly four times higher among Alaska Natives — the only racial or ethnic group where cases overall are not declining. In fact, cases are increasing 2 percent each year and remain the most commonly diagnosed cancer in this group.
Possible contributing risk factors for cases in this population, according to Siegel’s study, include vitamin D deficiency from less sun exposure, smoking, obesity, and a diet high in smoked fish and low in fiber, fruits, and vegetables.
The disparity between cases and deaths is more striking among black Americans, whose cases are 21 percent higher than 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 and 2018 — up from 25 percent a decade earlier — but three-year survival rates for black patients have plateaued at 22 percent, probably due to less access to improved treatments, Siegel and her co-authors write.
Geographic disparities are similarly caused, at least in part, by higher rates of smoking and obesity, as well as lower income and poorer access to health care, Siegel said. Both cases and mortality are lowest in the West and highest in the Appalachian Mountains and parts of the South and Midwest.
“If you look at a county-level map of poverty and county-level colorectal cancer mortality, they’re strikingly similar,” Siegel said. Obesity and poor diet are more common among lower-income people, especially since processed foods are cheaper and less likely to spoil than fresh foods, Siegel said.
Another factor contributing to the differences is insufficient information about screening options besides colonoscopy, Naik said. Colonoscopies require visits to centers that are more sparse in Alaska and rural areas. Colonoscopies typically also involve anesthesia, which means the patient has to be off work and someone else, who may also need time off from work, have to drive them home—all of which are more difficult for those on low incomes.
“Although colonoscopies are a gold standard for screening for colon cancer, it is not the only modality,” Naik said. “We also have chair-based testing that can be done in the comfort of your own home.” Although providers have a critical role to play in promoting screening, “healthcare systems really need to do a better job of engaging communities at a programmatic level,” he said he.
Ness goes even further. “The biggest cause of differences in colorectal cancer incidence and mortality remains low screening rates among uninsured, low-income individuals,” he said. “Until we commit to the concept and practice of universally available primary care, including colorectal cancer screening, in the United States, we will continue to see disparities in health outcomes.”