Researchers have found that diet-derived molecules known as metabolites may be the main drivers of early-onset colorectal cancer risk, especially those associated with red and processed meat, according to a recent study published by Jayakrishnan et al in npj Precision Oncology.
Background
Despite the success of monitoring and screening for colorectal cancer, physicians may be able to take a different approach with younger patients.
“At the end of the day, it’s impractical to apply our care models for those over 60 to younger adults simply because we cannot give everyone in the system yearly colonoscopies,” explained senior study author Suneel Kamath, MD, a gastrointestinal oncologist at the Cleveland Clinic. “What is much more feasible is to give everyone in the system a simple test to measure a biomarker that determines their colorectal cancer risk. Then we can give the most at-risk individuals appropriate screening,” he added.
In a previous study, the researchers identified differences in the metabolites of early- vs average-onset colorectal cancer, whereas separate research has identified differences in the gut microbiome between younger and older adult patients with colorectal cancer. These studies have provided many potential directions for investigating early-onset colorectal cancer; however, when additional factors are involved in cancer risk, it often becomes challenging to understand how they influence cancer risk. Interactions between these factors—including when gut bacteria consume metabolites and produce their own—make it even more complex.
Study Methods and Results
In the recent study, the researchers provided large-scale analyses of metabolite and microbiome data sets from patients who received care for either early- or average-onset colorectal cancer. The researchers developed an artificial intelligence (AI) algorithm to combine and analyze data from existing studies and clarify what factors are most relevant for future examination. Notably, the analysis revealed that differences in diet identified through analyzing metabolites accounted for a significant proportion of the differences observed between the early-onset and later-onset patients.
“Researchers … have begun to focus on the gut microbiome as a primary contributor to colorectal cancer risk, [b]ut our data clearly show that the main driver is diet,” emphasized co–lead study author Naseer Sangwan, PhD, Director of the Microbial Sequencing & Analytics Resource Core at the Cleveland Clinic. “We already know the main metabolites associated with [early]-onset risk, so we can now move our research forward in the correct direction,” he noted.
The researchers suggested it may be easier to identify at-risk patients by counting the metabolites in their blood compared with sequencing the bacterial DNA in their stool for different microbes. “It can actually be very complicated and difficult to change your microbiome. While it’s not always easy, it is much simpler to change your diet to prevent colorectal cancer,” Dr. Kamath detailed.
Younger patients with colorectal cancer had higher levels of metabolites associated with the production and metabolism of the amino acid arginine and with the urea cycle compared with older patients. These differences may be correlated with long-term consumption of red meat and processed meat.
Conclusions
The researchers emphasized that one of the most effective strategies individuals younger than age 60 can follow to prevent colorectal cancer may be to discuss their diets with their physicians.
The researchers are currently analyzing national data sets to validate their findings in patients across the country. They anticipate finding that arginine and urea cycle metabolites—and by proxy, red and processed meat overconsumption—will be elevated across younger patients with colorectal cancer nationwide. They subsequently plan to evaluate whether certain diets or commercially available drugs that regulate arginine production and the urea cycle may help to prevent or even treat early-onset colorectal cancer.
Although additional research may be needed to understand how dietary factors can cause colorectal cancer, the findings may inspire adjustments in patient care. “Even though [we] knew before this study that diet is an important factor in colorectal cancer risk, [we] didn’t always discuss it with [our] patients during their first visit. There is so much going on, it can already be so overwhelming,” underscored Dr. Kamath. “Now, [we can] make sure to bring it up [with our] patients, and to any healthy friends or family members they may come in with, to try and equip them with the tools they need to make informed choices about their lifestyle,” he concluded.
Disclosure: For full disclosures of the study authors, visit nature.com.
