Like so many in her field, The Ohio State University oncologist Ning Jin is alarmed by the number of patients in their 30s and 40s with late-stage cancer in their lower digestive tract. It's not just that these patients are decades younger than what had been typical for colorectal cancer; Jin says the tumors themselves are also more stubborn to treat.

"Even though we treat young patients with more aggressive chemo — more chemo or more surgery — patients' outcomes are not necessarily better," Jin says. And the disease has become the top cancer killer among people under 50 — even as death rates decline in older age groups.

Advances in science in recent years have made many cancers more treatable and survivable — but not colorectal cancer, which has become more lethal, striking people at younger ages. And it's occurring more often too.

What's causing the rise in cancers among younger patients — not just of colorectal, but all forms — is a huge medical mystery. Increasingly, doctors suspect that the gut's microbiome is a key actor behind these forms of cancer in particular.

Patient advocates say it's critical that more people — especially young adults with a family history of these cancers — get diagnostic testing. Preventive testing isn't regularly recommended and covered by insurance until age 45. But young people should keep an eye out for symptoms, advocates say, and raise the issue with their doctor.

A generational change

Genetics play some role in colorectal cancers. Jin says as many as a fifth of patients have hereditary markers — like a genetic mutation for Lynch Syndrome — that increase the risk of getting colorectal cancer, among others. But genetics do not explain what drives the vast majority of cases — about 80% of colorectal cancers.

So Jin and others have concluded: "There must be some environmental factors or changes."

It is highly unusual to see dramatic changes in disease patterns within a single generation. But that's precisely what veteran oncologist Dr. John Marshall, head of clinical research at the Lombardi Cancer Center at Georgetown University has observed.

"Thirty-plus years ago, when I first started, no one — no one; zero number of patients — were in my clinic under the age of 50 with colon cancer," he says. "And now it is almost half of the patients that I see."

Marshall says there are other changes in disease pattern, too: Earlier onset tumors tend to show up differently — more tumors are found near the rectum, lower in the tract.

Clearly something correlating with a generational change is shaping this disease.

Potential culprits

Experts suspect several factors may be leading to these more frequent, virulent cancers: One is our greater reliance on ultra-processed foods, as well as plastics and chemicals that can leach into water and our bodies. Plus, there are other notable lifestyle changes: As a population, we are not as active as we used to be.

Researchers' prevailing theory is that all of those factors act on our gut — specifically, says Marshall, the composition of our microbiome, and the bacteria and myriad microorganisms living there. And a disturbed microbiome may contribute to colorectal cancer. His own research focuses on early and late-stage treatments for the disease.

"The way I think of it is, it's our soil; it's a very important part of our interface with the world," Marshall says, because digestive organs' primary role is to help incorporate the things we eat into our bodies.

"What I think is that we have somehow altered the soil in some way so that it's now causing this phenomenon of colon cancer," he says. "It may be causing other diseases, too. But the most striking one is colon cancer."

Chemicals we're exposed to in our environment — such as in some laundry detergents, or processed foods — may strip away the protective mucus layer, that lines the gut and serves as a partial barrier against the things moving through it.

Losing that shield is like tearing down slats in a fence; it leaves openings that can get inflamed, says Jin, the Ohio State specialist.

"The microbes can cause DNA damage and cause leaky gut, or other chemicals can disrupt that mucus protective layer and then cause leaky gut," she says.

Searching deeper

While it's unclear exactly how disturbances in the microbiome could lead to cancer, one study found a link between the DNA-damaging toxin, colibactin, made by certain strains of E. coli and other bacteria, and colon cancer among younger patients.

But studying the interactions that happen within the body's microbiome is complex. For one thing, Marshall notes, our mouths, stomachs, and gut have different chemistries and microbiomes — all of which may create conditions that contribute to tumor formation.

And, he says, there is no accurate way to gauge whether one's microbiomes are on the healthy track: "We don't know how to test it, we don't know how to make a good one."

And while scientists have their suspicions about some of the mechanisms that damage the gut, it remains hard to isolate which factor triggers the formation of cancer, and to know when or how to prevent that exposure. Jin says more controlled studies to examine each factor are needed.

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