It’s one of the mysteries that has puzzled cancer epidemiologists: Why are younger and younger people becoming sick with colorectal cancer?

The latest national cancer statistics from the American Cancer Society show adults under the age of 55 have seen their colorectal cancer rate increase 2 percent per year since the mid-1990s. Overall, those born in 1990 have double the risk of developing colon cancer and four times the risk of getting rectal cancer compared to those born around 1950. That’s why, in response to the alarming trend, the ACS in 2018 lowered the recommended age for routine colorectal cancer screening to 45 from 50.

“It’s not like the problem is bad and has stabilized,” said Thomas Weber, the director of surgical oncology at New York’s Northwell Health, who organizes an annual summit for researchers trying to solve the mystery. “The problem has continued to worsen.”

Related 4 behaviors that may cut the risk of cancer by 30 percent

A recent study, published in Lancet Gastroenterology & Hepatology, suggests the trend may be global. Looking at long-term data on colon and rectal cancer incidence in developed countries — such as Denmark, Canada , New Zealand, and the UK — the authors found increases in people younger than 50 during the most recent decade they analyzed (2004 to 2014).

Researchers have a couple of potential explanations for what’s going on: the rising rates of obesity and factors that shape the microbiome in early childhood. Since 1980, the obesity prevalence has doubled in more than 70 countries around the world. Thirty-nine percent of US adults, are now obese, along with 19 percent of children and adolescents.

Another recent JAMA study looked at 85,000 women and found a link between a higher body weight, particularly obesity, and a greater risk of colorectal cancer.

But not so fast: One of the JAMA paper’s authors, Washington University School of Medicine cancer epidemiologist Yin Cao, warned this study isn’t the final answer: “I think we are getting closer but this is not the final answer for [the mystery].” Here’s why.

The link between obesity and colorectal cancer

Colorectal cancer is the third most common cancer diagnosed in the United States, with a lifetime risk of 4 to 5 percent in men and women. While it used to be a disease that mainly surfaced after middle age, the shift to younger and younger ages has alarmed researchers. And not only are people in their 20s and 30s increasingly being diagnosed with the disease; they’re also dying from it.

The main reason obesity is thought of as a potential driver of early-onset colorectal cancer is because it’s associated with inflammation in the body.

You can think about inflammation in two ways. There’s helpful inflammation, as with your body’s immune response to an attack by a foreign invader — your skin reddens and heats up to fight off bacteria in a cut.

There’s also harmful, or chronic, inflammation: when your body’s inflammatory response goes into overdrive, hampering its ability to fight off viruses and disease. One measure of it is a blood marker called C-reactive protein (CRP). Researchers have found associations between higher levels of CRP and various chronic illnesses, including cancer, arthritis, cardiovascular disease, and diabetes. People who are inactive or obese or who eat an unhealthy diet seem to have higher levels of CRP in their systems too.

The JAMA study looked at 85,000 women aged 25 to 42 who were followed from 1989 to 2011 as part of the ongoing Nurses’ Health Study II. The researchers mapped early-onset colorectal cancers against body mass index (BMI) — both current and at age 18 — to figure out whether having a higher BMI at any point in a person’s life was associated with greatest colorectal cancer risk before age 50. And they found strong associations.

The 114 women who developed colorectal cancer in the study tended to have a higher BMIs. Their risk also increased the higher their body weights climbed. So people with obesity (a BMI of 30) had nearly double the risk of early-onset colorectal cancer compared with women in the normal BMI range (18.5 to 22.9). In other words, it looked like as obesity rates climb, so too does colorectal cancer risk.

Why this mystery is hard to solve

But the impact of obesity on cancer risk is pretty hard to untangle from other behaviors or attributes of people with obesity, like diet. Researchers have uncovered strong associations between Western-style, pro-inflammatory diets — heavy in processed meat, red meat, organ meat, sugary beverages, and refined grains — and a higher risk of colorectal cancer. Two papers, published May 29 in the BMJ, also found links between a greater consumption of ultra-processed foods and higher risk of both cardiovascular diseases and mortality from any cause, including cancer.

It’s possible the heavier people in the JAMA study followed a diet that was more inflammation-promoting.

What’s more, the study only looked at a subset of cases. “There were 114 cases under the age of 50 [in the study], and there are some 16,000 cases a year of colorectal cancer of people under the age of 50 in the US,” Weber said.

So while obesity may play a role in driving this alarming trend, it’s probably not the entire explanation. Weber added: “Many, many providers are struck by how fit and active many of their young colorectal cancer patients are. And this includes the fact the vast majority of these cases have nothing to do with hereditary syndromes.”

That’s why other researchers are looking at whether colorectal cancer in young people may be the result of exposures to certain things in early childhood.

A new analysis of data from American Cancer Society cancer registries adds heft to that line of inquiry. The researchers found early-onset colorectal cancer has been rising most rapidly in Western states in the US — such as Colorado and Washington — where obesity rates are low and healthy behaviors are common.

“This finding suggests that early life exposures in addition to the ‘usual suspects’ [such as obesity] may be contributing to the rise in early onset disease,” said the study’s lead author, the American Cancer Society’s Rebecca Siegel, in a press release. “Future studies should explore novel risk factors for colorectal cancer in young adults.”

Franklin Berger, research and outreach director at the University of South Carolina, penned a Conversation article featuring a similar argument. “There is persuasive evidence that features of early life contribute to risks for a number of adverse health effects that occur in later childhood, teen ages, and even in young adults,” he wrote. This can include things like antibiotic treatments, whether a baby was born vaginally or through a C-section, stress, and again, diet and nutrition.

The idea is these factors may alter the microbiome — the ecology of diverse bacteria lining the intestines and colon. The trillions of microbes “undergo many changes during the period between birth and ages 3 to 4, and are highly susceptible to perturbation by the kinds of exposures listed above,” Berger writes. Again, the science here is still in its early stages — but it’s an area to watch.

For now, patients — including young adults — should be aware of this emerging trend, and the signs and symptoms of colorectal cancer.