ABOVE: Adenomatous polyp

Rachel Winegar, a mother of three from Colorado, has had trouble with her digestive system for as long as she can remember. So when she neared 30 and her problems intensified, colorectal cancer did not cross her mind. Her doctor figured it was perhaps a chronic condition like celiac disease, ulcerative colitis, or Crohn’s disease. She was suffering: “rectal bleeding even while passing gas, full feeling, bloated, nauseous, low energy, feeling of sitting on something, pencil-thin stools,” she writes in an email to The Scientist.

After she finally went to a doctor, Winegar was scheduled for a colonoscopy. But instead of finding evidence for any of those conditions, her doctor discovered a mass the size of Winegar’s palm in her rectum, she recalls. It was stage 4 cancer. “My husband and our three kids and I have had our lives turned upside...

Although still rare, affecting roughly 4 percent of adults over their lifetimes, according to the National Cancer Institute, colorectal cancer is becoming increasingly common in young adults, even as the incidence among older people is declining. The first reports of a rise among younger patients emerged a decade ago. “We thought this would level off with the newer data, but it continues to go up,” says Darren Brenner, a molecular cancer epidemiologist at the University of Calgary.

I definitely see patients who are vegetarians, they run marathons, they’re skinny, so it’s not exclusive.

—Nancy You, MD Anderson Cancer Center

Brenner and his colleagues’ recent analysis of Canadian national cancer registry data found that the incidence of colorectal cancer diagnoses among women under 50 increased annually by nearly 4.5 percent from 2010 to 2015. Canadian men under 50 experienced an average per-year increase of nearly 3.5 percent from 2006 to 2015. “Among males and females, we are seeing the highest-ever recorded rates among most recent birth cohorts,” he says. Of the country’s population of 37 million, nearly 12,000 women and nearly 15,000 men of all ages were diagnosed with colorectal cancer in 2017, according to the Canadian Cancer Society.

A recent study in the journal Cancer described a similar trend among Americans, the figures being a little higher for rectal cancers than colon cancers. In 2004, 10 percent of diagnoses were in people under age 50, compared to 12 percent in 2015. The rise is not restricted to North America: In May, one analysis found significant increases in colorectal cancer among people under 50 in Denmark, New Zealand, and the UK over the last decade. Similarly, a study of 20 European countries found that over the past decade, the incidence of colorectal cancer had increased by nearly 8 percent per year among people in their 20s, by 5 percent for people in their 30s, and by 1.6 percent for those in their 40s.

Nowadays at the University of Texas MD Anderson Cancer Center, one in three new colorectal cancer diagnoses involves patients between 18 and 50 years old, according to Nancy You, a surgical oncologist there. What worries her in particular is that young adults are disproportionately affected by rectal cancer, which requires more complex treatment than cancer of the colon, she writes to The Scientist in an email. In addition, they are disproportionately already at stages 3 or 4 at diagnosis—likely due to a lack of understanding of the disease in young people among patients and physicians, she says. The trends call for an urgent need to raise awareness of the issue and to understand its underlying causes. “It’s a really hard question to answer,” she says.

The many factors contributing to colorectal cancers

Generally speaking, a small proportion of colorectal cancers—around 5 percent—are hereditary, including conditions such as Lynch syndrome, which is caused by mutations in genes responsible for repairing errors in DNA replication. Another 20 percent or so have a family history of colorectal cancer, although it’s not clear whether it’s predominantly genetic or environmental factors that cause the disease to aggregate in some families.

Most colorectal cancers occur in people who don’t have a family history or a known genetic predisposition, as is the case with Winegar. For these sporadic cases, different theories have emerged for the causes, including gut microbiome changes and a sedentary lifestyle. For instance, evidence published earlier this year linked prolonged time spent sitting watching TV with an increased risk of developing the disease in young Americans. General risk factors for colorectal cancer also include smoking and heavy alcohol consumption.

The tumor can just directly eat the sugar that you are eating. That’s unique to colorectal cancer.

—Marcus Goncalves, Weill Cornell Medical College

Given that the increase in cases in young adults has occurred within a relatively short timeframe, it’s most likely driven by environmental risk factors, rather than genetic changes in the population, according to Brenner. “The likely culprits are probably a combination of major lifestyle and exposure trends that have changed over the past forty years,” he says.

Some researchers blame diet-related changes in recent decades. “We know that people in those younger groups are eating less fiber and are eating more processed foods than previous generations have,” Brenner says. These are known risk factors for colorectal cancer, as well as processed meat and red meat. In addition, obesity rates are climbing in young populations, which several studies have linked to the rise in colorectal cancer among young adults.

“Colorectal cancer is one of the most sensitive [cancers] to diet,” notes endocrinologist Marcus Goncalves of Weill Cornell Medical College in New York, whose research focuses on the effects of diet on cancer.

Although the precise links between obesity and colorectal cancer are unclear, he sees several ways in which obesity could fuel tumor growth. By increasing fat reservoirs across the body and near the tumor, obesity could provide cancerous cells with fuel to grow. Obesity can also predispose a person to hormonal changes such as high amounts of insulin and estrogen, which can increase the rate of cell growth. The condition also leads to systemic inflammation of body tissues, releasing cytokines that further spur tumor growth. Dietary habits can also alter bacterial populations in the gut, which could affect tumor growth by changing the levels of metabolites and hormones, he adds.

See “Breaking the Cancer-Obesity Link

Sugar intake may also be an important factor. “The tumor can just directly eat the sugar that you are eating. That’s unique to colorectal cancer,” Goncalves says. Recently, he and his colleagues conducted a study in mice that had a genetic predisposition for colorectal cancer, and fed them high-fructose corn syrup. In treated animals, those tumors became much larger and appeared to be more aggressive than in control animals that didn’t receive syrup. “But they did not become obese, so you can tease apart the [independent] effect of sugar,” he explains.

Colorectal cancers originate from benign polyps, or adenomas, which can become cancerous if not removed. Fructose in addition to glucose acts as a catalyst for glucose metabolism, which cells use to fuel the construction of macromolecules such as proteins, DNA, and lipids. In excess, these sugars could cause benign polyps to become cancerous. As cells grow and proliferate rapidly, this could increase the likelihood of new mutations to arise, such as in genes that regulate the cell cycle. “Our work would suggest that if you did have a benign polyp, and then you feed it a bit more sugar, that polyp could become cancerous faster,” Goncalves adds.

You, the MD Anderson oncologist, is wary of focusing too much on particular risk factors. “I definitely see patients who are vegetarians, they run marathons, they’re skinny, so it’s not exclusive,” she says. “The unfortunate reality [is that] many young people who ‘have done everything right’ are being diagnosed” as well, she adds.

Awareness needed for colorectal cancer in the young

Colorectal cancers in younger patients are often at advanced stages at the time of diagnosis. According to recent results of a social media survey of 1,195 colorectal cancer patients and survivors under 50, 71 percent said they were diagnosed at stage 3 or 4. “There’s a real disparity for them in being diagnosed in a timely manner,” says Ronit Yarden, the lead author of the research and the director of medical affairs at the Washington DC–based patient advocacy group Colorectal Cancer Alliance (CCA), which conducted the survey.

“What’s most devastating with colorectal cancer is that if caught early, it could be preventable, or at least the survival rate would increase significantly,” Yarden says. However, there are several major barriers to young adults in getting diagnosed early.

Uninsured young people with symptoms of colorectal cancer typically don’t have access to a timely colonoscopy, which is considered the gold-standard diagnostic tool for colorectal cancers. But even for those with insurance, it can be difficult to get a colonoscopy because of the way US insurance companies classify the procedure: If a doctor finds no polyps in the colon that have to be removed, most companies will consider that a preventive procedure for people under 50 with symptoms, Yarden explains. But once a polyp is found and removed, even if it’s benign, payers typically consider that a diagnostic test, and as such it is often subject to various deductibles and premiums. “Some people who are maybe underinsured may not want to go and check themselves because they’re afraid the cost will be increased if they find something,” she says. “That’s a loophole we have here in the US.”

Within the medical community in the US, there have been ongoing debates about how to adapt screening guidelines to the rise in cases among young people, You says. Last year, the American Cancer Society (ACS) reduced its recommended screening age for colorectal cancer from 50 to 45, as most cancers that occur before 50 are during people’s 40s. Some states have adopted that standard, but others are waiting for the American Preventive Services Task Force to adopt the ACS’s guidelines, Yarden says.

The fear around having a colonoscopy, an invasive procedure, may also deter people from going to the doctor. There are other, non-invasive screening methods available—such as fecal immunochemical tests—but a colonoscopy is considered the most efficient because polyps can be immediately removed during the visit, You says.

Many young people may be simply unaware that symptoms such as rectal bleeding at a young age could be caused by colorectal cancer, Yarden adds. That was the case with Rachel Winegar. In fact, 41 percent of the CCA’s survey respondents reported that they waited at least six months after experiencing symptoms before talking to a doctor.

This may also be due to a lack of awareness among physicians. According to the survey, 67 percent of respondents saw at least two doctors before getting a correct diagnosis. “My doctors weren’t looking for colon cancer,” wrote one respondent. “My symptoms were pretty obvious in hindsight, but I don’t think they are used to seeing this diagnosis in young people.” 

“Even though it’s [still] only ten percent that are young-onset colorectal cancer, that is still significant,” Yarden says. “Patients need to be aware of the symptoms and listen to their body and sometimes insist on getting a second opinion until getting checked thoroughly.” 

Winegar, who says she’s experienced preliminary positive results after receiving a course of the anti-cancer drug Stivarga at a treatment center in Mexico, agrees. “People need to know what’s ‘normal’ and what’s cause for concern.” 

Katarina Zimmer is a New York–based freelance journalist. Find her on Twitter @katarinazimmer.

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