The recent death of Dawson’s Creek star James Van Der Beek from bowel cancer, aged just 48, highlighted a worrying trend: cases of early-onset cancer are rising.
Research recently published in The Lancet Oncology found that the incidence of the disease in people under 50 has risen in 27 out of the 50 countries assessed over the past 10 years. Such a rise can’t easily be explained by genetic risk factors.
“It’s very concerning,” says Dr Trevor Lawley, a researcher at the Wellcome Sanger Institute and one of the scientists tasked with trying to understand what’s behind it. “There are several hypotheses that we’re exploring, but we still need more data.”
It remains unclear if there’s a single culprit or a combination of factors driving the rise in cases, but, right now, these are the main theories.
Obesity
Adolescent obesity is a known risk factor for early-onset bowel cancer, while health conditions such as type 2 diabetes and metabolic syndrome are also thought to make people more vulnerable to developing the disease.
“Obesity is a well-established risk factor for colorectal cancer at all ages,” says Peter Campbell, professor of epidemiology and population health at Albert Einstein College of Medicine in New York.
“Excess body fat promotes chronic inflammation and metabolic changes, including elevated insulin and related growth-factor signalling. Those conditions can encourage the development and growth of precancerous polyps and cancers in the colorectum.”
But, although there are rising numbers of people under 50 who are overweight or obese, Campbell says that this alone isn’t sufficient to explain the increase in bowel cancer. One analysis of a group of people with early-onset bowel cancer, for example, concluded that obesity only accounted for around 13 per cent of cases.
Instead, it appears that other key risk factors are involved, some of which emerge surprisingly early in life.
Gut bacteria
Cancer does not develop quickly. The transition from initial DNA damage to the formation of a tumour can play out over years or decades. So, in an attempt to understand the origins of bowel cancers that emerge in early-mid adulthood, Lawley and others are studying the microbiomes of babies.
The strongest causative explanation for early-onset bowel cancer so far is a toxic enzyme called colibactin.
It’s known to be capable of inflicting distinct patterns of DNA damage on cells in the colon, damage that’s hard to repair. A study published in Nature last year found that colibactin-related DNA mutations are 3.3 times more common in bowel cancer patients under the age of 40, compared with those over 70.
There are a number of species of gut bacteria that are capable of producing colibactin, opportunistic pathogens that include strains of E. coli, Klebsiella pneumoniae and Citrobacter koseri.
It’s thought that a proportion of the population acquires these pathogens in their guts during their earliest stages of life, making them more vulnerable to experiencing DNA damage and developing cancer many decades later.
“My lab has this large database of microbiomes of babies around the world. [By looking at it] we could say that 25 per cent of babies born in the UK, for example, have colibactin in their gut microbiome,” says Lawley.
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A major theory is that more babies today are acquiring pathogenic gut bacteria in their colons, compared to previous generations. But why?
Some researchers blame the increased use of antibiotics in early childhood – drugs that can inadvertently wipe out large swathes of useful gut microbiomes and make the gut microbiome more vulnerable to being colonised by malevolent invaders.
Others wonder whether it might be related to the growing prevalence of C-section births, the increased use of formula milk or something else entirely. “These are all things we’re exploring,” says Lawley.
Ultra-processed foods
Complicating matters is the fact that there are likely to be many people with colibactin DNA mutations in their guts who don’t develop cancer.
This is because their immune system can spot the emergence of malignant cells and destroy them before they develop into a tumour. “You need the mutation [for cancer to develop], but the immune system is also important,” says Lawley.
Hence, another theory is that a diet rich in ultra-processed foods (UPFs) may be playing a role in the development of bowel cancer. Research published in Nutrition in 2021 has suggested that regular consumption of UPFs may dysregulate the immune system.
UPFs can also fuel the growth of pro-inflammatory gut microbes such as Fusobacterium nucleatum, which is thought to increase the risk of early-onset bowel cancer by helping tumours to evade the immune system’s surveillance.
Last year, a study by researchers at Harvard Medical School published in JAMA Oncology found that women who consumed up to 10 portions of UPFs a day had a 45-per-cent higher risk of having polyps (abnormal growths) in the lining of their guts, than women who consumed three servings a day. “These are the kinds of polyps that can precede colorectal cancer,” says Campbell.
Environmental toxins
The preceding three theories offer the strongest evidence to date, but researchers remain open to new ideas, including the possible role of environmental toxins, such as micro- and nanoplastics.
One study, reported in October last year, used stool samples from healthy volunteers to recreate models of their gut microbiomes in the lab, before exposing them to five common types of microplastics.
The scientists behind the study found that some plastic particles appear to be capable of changing the composition of the microbiome.
Frank Frizelle, professor of colorectal surgery at the University of Otago, Christchurch, has speculated that the accumulation of plastic in the gut may play some role in the development of bowel cancer in the young.
“The most likely way is that they allow the protective mucus layer that protects the bowel lining to be permeated in some way, like putting pin holes in a water balloon,” says Frizelle. “It’s unlikely that the plastics themselves are toxic, it’s more likely that they’re either a carrier [of harmful bacteria and chemicals they produce] or have a mucus-damaging effect.”
Potential solutions
Ultimately, there are still many unknowns, but as we learn more about the potential causes of early-onset bowel cancer, it’ll also lead to new solutions.
One idea is phage therapy, delivering viruses into the gut that feast on colibactin-producing bacteria and stop the production of this toxin in its tracks. Another possibility is to design probiotics that can nurture the growth of useful gut microbes and enable them to outcompete the colibactin-generating pathogens.
“There are companies out there who are working with phages, almost a sniper-like approach to try and take out the E. coli strains producing the colibactin,” says Lawley.
“We’re trying to use the databases of early life microbiomes, to identify species and strains associated with health that could be delivered so that they go in and colonise babies with a more depleted microbiome, in the first few months of life.”
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