Colon cancer is rising in young people

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Colorectal cancer should be on your radar: Today, one in five cases diagnosed occurs in people younger than 54, marking an 11 percent uptick in this age group over the past two decades. What, exactly, is fueling the surge in younger patients has perplexed scientists and medical professionals alike.

Colon cancer is rising among young adults. Here are signs to watch for.

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 study published by the American Cancer Society. Another study published in the Lancet Oncology suggests this trend is consistent among high-income countries.

There’s no clear explanation for this trend, but a paper published in Science in March 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,” says 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,” says 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, says 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 says.

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 says, 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 says. “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, says early onset disease is at least “partly explained by antibiotic usage in childhood and young adulthood, as shown most convincingly,” in a 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, says 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 says, 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,” says 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 says. 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 says. 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 says. 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, says 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 says. “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 says.

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 says. “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.”

What researchers discovered in colon cancer patients

For years, however, experts have suspected that colibactin, a toxin produced by E. coli and other bacteria that can damage DNA, could be involved. Now, a new study published in Nature has identified a strong link between childhood exposure to colibactin and colorectal cancer in patients under the age of 40.

Here’s how the study expands scientists’ understanding of the microbiome’s influence on colorectal cancer development, plus how a focus on colibactin could pave the way for earlier detection and new prevention strategies.

The researchers initially designed the study to broadly explore why people in different countries develop colorectal cancer at different rates, so the colibactin observation was “somewhat incidental,” says lead study author Ludmil Alexandrov, a professor of cellular and molecular medicine at the University of California, San Diego.

He and his team analyzed blood and tissue samples from the tumors of nearly 1,000 colorectal cancer patients across 11 countries, including Canada, Japan, Thailand, and Colombia. They used DNA sequencing technology to identify cellular mutations, or genetic changes that can help cancer form, grow, and spread.

“Different carcinogens leave this characteristic pattern of mutations, which we call mutational signatures,” Alexandrov explains. “The simplest example is if you smoke cigarettes, you get a specific pattern of mutations across your lung cells.”

Alexandrov and his team found that people diagnosed with colorectal cancer under the age of 50 had a “striking enrichment” of mutations associated with colibactin. The younger the person was, on average, the higher the prevalence of these signatures. Those diagnosed with colorectal cancer under age 40 were about three times more likely to have colibactin-driven mutations than those diagnosed after age 70.

“When we sequence cancers, we see this archeological record of everything that happened in that person’s lifetime,” Alexandrov says. Meaning, scientists can figure out the approximate timing of when specific mutations took hold in the gut.

The study’s results suggest that the participants’ colibactin exposure happened before they turned 10. This early “hit” to the gut microbiome seemed to put people 20 to 30 years ahead of schedule for developing colorectal cancer, Alexandrov says. Rather than being diagnosed in their 60s or 70s, they faced the disease in their 30s or 40s.

Cynthia Sears, an infectious disease expert and professor of oncology at the Johns Hopkins University School of Medicine, who was not involved in the study, believes the study was done “carefully and thoroughly,” but also leaves questions unanswered. “We don’t understand the biology of these organisms and the circumstances that allow them to be mutational,” she says.

Alexandrov agrees. He says this new study shows a “strong association” between childhood colibactin exposure and early-onset colorectal cancer. However, proving that colibactin actually causes colorectal cancer would be “very complicated.”

How colibactin could lead to colorectal cancer

Colibactin is a genotoxin—think of it as a weapon certain bacteria deploy to protect themselves against other microbes. Experts theorize that, in some people, these bacteria become dominant and then start hurting their hosts, Alexandrov explains. Once they colonize the colon, they can latch onto healthy tissues, attack cells, and generate DNA mutations.

But not everyone with colibactin-producing bacteria winds up with colorectal cancer—estimates show 20 to 30 percent of people harbor these strains. So what’s prompting the bugs to go rogue in certain individuals? “We think something is happening to give them an advantage over the other bacteria,” Alexandrov says.

He cites previous studies that suggest people in Westernized countries (particularly urban areas), like the U.S. and parts of Europe, tend to have a higher prevalence of colibactin-producing bacteria in their guts than those in more rural or non-industrialized regions. “To me, this is a window of opportunity to zero in on environmental influences in different sectors of the world,” Sears says.

In particular, evidence suggests that a Western diet—typically higher in red and processed meats, added sugar, and refined grains and lower in fruits and vegetables—is associated with a higher risk of colorectal cancer. As for the reason why colibactin, specifically, could be more “mutagenic” in the setting this diet creates in the gut? “We just don’t have this information,” Sears says.

The new study didn’t analyze the participants’ individual cancer risk or track changes in their environment or diet, so any combination of these components could be at play. Alexandrov and his team suspect factors that can substantially alter a person’s immune system and microbiome in their earliest years, like whether they were born via a C-section or vaginally, took antibiotics, were breastfed or formula-fed, or were fed a lot of processed foods.

Some colibactin-producing bacteria may also trigger an immune response that further injures the cells. Those are the strains that “get us into trouble,” Sears says. But it’s “extremely complex” to figure out what makes these bacteria stick in different parts of the gut. “The rectum is different than the sigmoid colon,” she explains. “Each of these regions has a somewhat different biology and predilection to tumor formation.”

Where the research goes from here

Alexandrov and Sears agree that longitudinal data is needed. Ideally, researchers would follow people in early life, give them probiotics designed to target colibactin-producing bacteria, and then track whether participants develop the associated mutations, and thus, early-onset colorectal cancer.

“If we can create the right probiotic that would bump off the bad actors, that might be a prevention strategy that would be easy and not harmful to people,” Sears says.

Alexandrov and his team are looking into future studies that explore this possibility. He also believes they could design a stool test that pinpoints colibactin-related mutations. If this DNA damage is detected in the test, then the individual would be encouraged to start colorectal cancer screening earlier—say, in their 20s versus their 40s.

All that said, Sears believes focusing on colibactin alone likely isn’t the “holy grail” solution to the rise in early-onset cases. “We don’t want to be too short-sighted about the spectrum of the research that we do,” she says.

Until we have more data, focusing on the lifestyle changes you can control is key; Sears points to eating a Mediterranean-style diet, staying active, quitting smoking, and cutting back on alcohol.

Awareness is also paramount: Young adults—as well as many medical professionals—are quick to brush off colorectal cancer symptoms like persistent abdominal pain, unexplained weight loss, and rectal bleeding. As Alexandrov stresses, “they should be aware that it may be something quite serious,” because the sooner the tumors are detected, the easier they will be to treat.

The FDA approved the first colon cancer screening blood test. Could it replace colonoscopies?

With colon cancer the second largest cancer killer in the United States, experts have long urged eligible adults to undergo regular screenings, but many avoid them because they are unpleasant, invasive, and time-consuming. That’s why it’s big news that the U.S. Food and Drug Administration has approved the first blood test screening option, allowing people to check for colon cancer in a similar way doctors assess their cholesterol and blood sugar.

The test, called Shield, uses blood drawn by a medical professional and sent to a lab. The test detects signs of colorectal cancer—proteins associated with colon cancer and DNA from tumor cells—in the bloodstream. Shield has been available in the U.S. by prescription since 2022 but gaining FDA approval makes it more likely the method will be covered by private insurance and Medicare.

Survival rates are significantly higher when colon cancer is detected early. Some 91 percent of people live five years or longer if the cancer is removed when it is still restricted to the colon. If discovered after the colon cancer has spread, only 15 percent of patients live this long. Yet only 35 percent of Americans with the disease are diagnosed at the earlier stage.

Colon cancer screening, which leads to earlier detection, is so effective that several years ago the U.S. Preventive Services Task Force lowered the recommended age of screening from 50 to 45 for people of average risk. Yet studies show only about two-thirds of Americans are up to date with the screening recommendations.

According to Shield’s manufacturer, Guardant Health, some people avoid getting tested because they dislike the time-consuming nature and discomfort of colonoscopy or flexible sigmoidoscopy—where a scope examines only the lower intestines—both of which require bowel cleansing preparations, or the need to handle samples for stool-based tests.

“A blood test like this is likely to have uptake for certain individuals that meet screening guidelines but are not currently being screened,” says Michael Cecchini, a medical oncologist at Yale Cancer Center. The test is especially valuable in places in the U.S. and globally that lack access to invasive modalities like colonoscopy, he says.

Still, Cecchini emphasizes that more studies are needed to determine whether the blood test reduces colon cancer mortality over time, which is the ultimate goal.

Colonoscopy may still be needed

The FDA’s approval follows the publication of a clinical trial testing the blood screen in the New England Journal of Medicinein March, which included more than 20,000 people in rural and urban communities across the country. Shield correctly identified 83 percent of people who had colorectal cancer, only slightly lower than the sensitivity of stool DNA tests.

But Shield did not identify many large polyps, some of which can later develop into cancer.

“One way to think about other screening modalities, such as a colonoscopy, is that while it can also identify cancers, it can remove pre-malignant polyps,” Cecchini says.

And people whose blood screen is positive still require a colonoscopy to confirm that a positive result was not false, which happens about 10 percent of the time.

Some worry that insurance companies might not fully cover colonoscopies that follow a positive blood test, as they are required to do by law for routine screening colonoscopies.

But experience shows this may not be a concern, says Prosper Abitbol, a gastroenterologist in Boca Raton, Florida. “Screening colonoscopies have been covered by insurance after positive results from Cologuard,” a stool DNA test, he says.

Experts say the most important thing is to choose a screening regimen from among the available options.

Americans ages 45 to 75 or older who are at average-risk for colorectal cancer should either have a colonoscopy, considered the gold standard, every 10 years; a flexible sigmoidoscopy or virtual colonoscopy every five years; a stool DNA test every three; another stool test annually; or the new blood test.

It is currently unclear how often the Shield test should be repeated, as it is not yet included in cancer guidelines. Studies evaluating various intervals to most accurately gauge the ideal “will take about 10 years,” says Aasma Shaukat, a gastroenterologist at New York University’s Grossman School of Medicine who has worked on screening guidelines from gastroenterology societies. Until then, the manufacturer will likely recommend whatever interval insurance will pay for, as is currently done for Cologuard, Shaukat says.

Even though a blood test may not be as comprehensive as some other methods, its simplicity is a major advantage, Cecchini says. “The ‘best’ screening test is the one that a patient is willing to do.”

Resources

nationalgepgraphic.com, “Colon cancer is rising in young people. Finally, scientists have a clue about why.” By Alisa Hrustic; nationalgeographic.com, “Colon cancer is rising among young adults. Here are signs to watch for.” By Alisa Hrustic; nationalgepgraphic.com, “The FDA approved the first colon cancer screening blood test. Could it replace colonoscopies?” By Alisa Hrustic;