Tragic news from Dawson’s Creek star James Van Der Beek, who recently succumbed to bowel cancer at just 48 years old, has brought attention to the alarming surge of early-onset cancer cases.
New research highlighted in Lancet Oncology indicates that the incidence of this disease among individuals under 50 has escalated in 27 out of 50 countries over the last decade—an increase that cannot be simply attributed to genetic factors.
“That’s very concerning,” states Dr. Trevor Rowley, a researcher at the Wellcome Sanger Institute. “While we have hypotheses we are examining, the need for additional data remains critical.”
It is yet unclear if a single factor is responsible for this rise or if a combination of elements is at play, but these are currently the leading theories.
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Obesity and Early-Onset Cancer
Adolescent obesity is among the recognized risk factors for early-onset colorectal cancer, along with conditions like type 2 diabetes and metabolic syndrome that can further heighten this risk. Onset of disease is increasingly attributed to these health issues.
“Obesity is a well-known risk factor for colorectal cancer across all age demographics,” asserts Dr. Peter Campbell, professor of epidemiology at Albert Einstein College of Medicine.
“Excess body fat leads to chronic inflammation and metabolic changes, which include elevated insulin levels and growth factor signaling—conditions that can foster the development of precancerous polyps and cancers in the colorectum.”
However, Campbell notes that while the number of individuals under 50 who are overweight or obese is rising, this alone does not fully account for the increase in bowel cancer cases. One analysis revealed that obesity was a contributing factor in only about 13% of early-onset colorectal cancer cases.
Thus, other significant risk factors likely play a role, some of which manifest surprisingly early in life.
The Role of Intestinal Bacteria
Cancer does not develop overnight. The progression from initial DNA damage to tumor formation can take years or even decades. To unravel the origins of colorectal cancer, especially in young adults, Rowley and his team are investigating the microbiomes of infants.
The leading theory posits that a toxic enzyme known as colibactin may be a key contributor to early-onset colorectal cancer.
This enzyme is known to cause unique patterns of DNA damage in colon cells that are notoriously difficult to repair. A study published in Nature found that colibactin-related DNA mutations were 3.3 times more frequent among colorectal cancer patients under 40 compared to those over 70.
Numerous gut bacteria species are known to produce colibactin, including Escherichia coli, Klebsiella pneumoniae, and Citrobacter coseri.
It’s believed that some individuals acquire these pathogens in early life, setting the stage for future DNA damage and increased cancer susceptibility decades later.
“My lab has amassed a significant database of baby microbiomes from around the globe. For instance, about 25% of infants born in the UK have colibactin in their gut microbiome,” Rowley shares.
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The prevailing hypothesis is that more infants are acquiring pathogenic enteric bacteria in their colons compared to earlier generations. But why?
Some researchers point to the rising use of antibiotics in early childhood. These medications can unintentionally decimate significant portions of the beneficial gut microbiome, facilitating invasion by harmful bacteria.
Others speculate that increased C-section births, reliance on formula feeding, or other factors may be contributing to this trend. “These are all avenues we’re researching,” Rowley notes.
Ultra-Processed Foods
Complicating the situation is the fact that many people may carry colibactin DNA mutations without ever developing cancer.
This phenomenon could be attributed to their immune systems effectively identifying and eliminating malignant cells before tumor formation occurs. “While a mutation is necessary for cancer development, the immune system also plays a crucial role,” Rowley explains.
Consequently, another theory suggests that diets high in ultra-processed foods (UPF) may influence the development of colorectal cancer. A study published in Nutrition in 2021 indicated that regular intake of UPF may lead to immune system dysfunction.
UPF may also encourage the growth of pro-inflammatory intestinal bacteria such as Fusobacterium nucleatum, which is believed to increase risk by enabling tumors to evade immune system surveillance.
Last year, a study conducted by researchers at Harvard Medical School, published in JAMA Oncology, found that women consuming up to 10 servings of UPF per day had a 45% higher risk of developing intestinal polyps compared to those who ingested just three servings daily. “Such polyps can precede colorectal cancer,” Campbell warns.
Environmental Toxins
While the three theories mentioned above have substantial backing, researchers continue to explore fresh hypotheses, including the potential impact of environmental toxins like microplastics and nanoplastics.
A study published last October recreated a gut microbiome model using stool samples from healthy participants, who were subsequently exposed to five common microplastics.
The findings suggested that particular plastic particles could alter microbiome composition.
Frank Frizell, a Professor of Colorectal Surgery at the University of Otago, speculates that plastic accumulation in the intestines may be linked to the rise of colorectal cancer among the youth.
“It’s plausible that they could penetrate the protective mucus layer of the intestinal lining, akin to poking a pinhole in a water balloon,” Frizell explains. “The plastics likely aren’t toxic in themselves, but they may act as vectors for harmful bacteria and chemicals or disrupt the mucus barrier.”
Potential Solutions
Ultimately, while many unknowns remain, further understanding of the causes behind early-onset colorectal cancer could pave the way for new solutions.
One avenue worth exploring is phage therapy, which involves introducing viruses into the intestine that target colibactin-producing bacteria, effectively halting toxin production. Another possibility is the development of probiotics designed to enhance the growth of beneficial gut bacteria, thereby counteracting harmful pathogens.
“Certain companies are exploring the use of phages to eliminate bacterial strains that produce colibactin,” Rowley notes.
“We’re leveraging a database of early childhood microbiomes to identify beneficial species and strains that could invade and prosper in babies with less diverse microbiomes during their initial months of life.”
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Source: www.sciencefocus.com
