Why are young adults getting colorectal cancer? E. coli may be a clue – National

Exposure to a bacterial toxin in childhood may be playing a key role in the global rise of early onset of colorectal cancer, according to a new study.

The study, published April 23 in Nature, found that a toxin called colibactin, produced by certain strains of E. coli that live in the colon and rectum, is capable of altering DNA.

The researchers from the University of California reported that early exposure to colibactin leaves a unique mark on colon cell DNA — one that could bump up your chances of getting colorectal cancer before 50.

However, it’s important to note that the study did not prove colibactin caused cancer, it only identified a link between mutations linked to the toxin and early-onset disease.

“These mutation patterns are a kind of historical record in the genome, and they point to early-life exposure to colibactin as a driving force behind early-onset disease,” said study senior author Ludmil Alexandrov, professor in the department of cellular and molecular medicine at the University of California San Diego.

“If someone acquires one of these driver mutations by the time they’re 10 years old, they could be decades ahead of schedule for developing colorectal cancer, getting it at age 40 instead of 60,” he said in a media release.

Colorectal cancer includes two types of cancers: cancer of the colon and cancer of the rectum.

Generally, it spreads more slowly than many other cancers, often lingering in the colon or rectum for months or even years before spreading elsewhere. That means if it’s detected early, treatment is usually very effective.

While colorectal cancer rates have been falling among older adults, they’ve been climbing in people under 50 — both in Canada and around the world — over the past few decades, for reasons that still aren’t clear.

If current trends continue, it’s projected to become the leading cause of cancer-related death among young adults by 2030.

“The fastest-growing subset of the population who get colorectal cancer, and primarily rectal cancer, are between the ages of 28 and 39 years old,” said Barry Stein, president and CEO of Colorectal Cancer Canada.

“And we don’t have a reason to understand why these people are being diagnosed or why they’re getting colorectal cancer in the first place.”

The question of why this is happening is what led the University of California researchers to dig deeper. Stein explained that there’s already some evidence linking gut bacteria to colorectal cancer — whether it’s a cause or just a correlation — and said this study adds another piece to the puzzle.

To help explain the medical mystery, the study’s researchers looked at 981 colorectal cancer genomes from patients with both early- and late-onset disease across 11 countries (including Canada) with varying colorectal cancer risk levels.

The researchers found that colibactin leaves behind DNA mutation patterns in colorectal cancer that are 3.3 times more common in adults diagnosed before 40 than in those diagnosed after 70, and these patterns are especially frequent in countries with high rates of early-onset colorectal cancer.

Previous studies, including earlier work from Alexandrov’s lab, have found colibactin-related mutations in about 10 to 15 per cent of all colorectal cancer cases.

Bu, these studies either focused on late-onset cases or didn’t differentiate between early- and late-onset disease. This latest study is the first to specifically highlight a significant increase in colibactin-related mutations in early-onset cases, the researchers said.

The researchers found that the damage caused by colibactin seems to kick in surprisingly early. By analyzing the molecular “timing” of different DNA mutation patterns, they were able to show that the mutations linked to colibactin tend to show up early in the process of tumour development, often during the first decade of life.

This means the colibactin-producing bacteria might be taking hold in children’s digestive systems early on, quietly altering their DNA in ways that could increase the risk of developing colorectal cancer later in life, long before any warning signs emerge, the study said.

Dr. Shuji Ogino, chief of the molecular pathological epidemiology program at the Brigham and Women’s Hospital in Boston, called the study findings “fascinating.”

“Cancer develops in a long-term process. So people have cancer at age 40, age 45 or age 60, right? They have a symptom, go to the doctor,” he said. “But in reality, it’s likely that the process starts earlier. We don’t know yet when it starts, but it could start quite early, even as a baby.”

And that’s what the study points to, he added.

Although it’s too early to tell, Stein said if there is a link between the bacteria and colorectal cancer, it may have “very profound effects.”

“For example, maybe these are things that we could look for when we’re doing screening for the disease in terms of preventing the disease in the first place,” he said. “Or maybe it’s something that, through treatment, through developing a vaccine or developing a drug, we can attack those types of bacterium, which could stop the cause of colon cancer.”

In the meantime, the researchers say there’s still a lot we don’t know — and this discovery opens the door to a whole new set of questions.

How exactly are kids being exposed to colibactin-producing bacteria, and is there a way to reduce or prevent that exposure? Are certain diets, environments or lifestyle factors making the body more hospitable to these microbes? And how can someone even find out if they already carry these kinds of mutations?

The team is actively digging into these questions. They’re exploring various theories, including whether probiotics could help safely wipe out harmful strains.