A new Cleveland Clinic study has identified diet-derived chemicals termed metabolites as the primary drivers of young-onset colorectal cancer risk, particularly those associated with red and processed meat. The NPJ Precision Oncology paper studied metabolite and microbiome datasets and found that discussing food with a doctor is an effective method for younger adults (>60 years) to prevent colorectal cancer.
 
Increased monitoring and screening for colorectal cancer is a very useful tool. Senior author and gastrointestinal oncologist Suneel Kamath, MD, suggests that despite the efficacy of these approaches, physicians should approach younger patients differently.
 
"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," he explains. "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."


Former clinical fellow Thejus Jayakrishnan, MD, and Naseer Sangwan, PhD, director of the Microbial Sequencing & Analytics Resource Core co-led the work. Researchers in Cleveland Clinic's Center for Young-Onset Colorectal Cancer provided large-scale analyses of patient data from individuals who received care for either young- or average-onset colorectal cancer at Cleveland Clinic.
 
This team's earlier work found disparities in the metabolites (diet-derived compounds) of young- and average-onset colorectal cancer, as well as differences in the gut microbiome between younger and older persons with colorectal cancer. These research suggested numerous new possibilities for exploring young-onset CRC. However, when more elements are involved in cancer risk, it becomes more difficult to grasp what's going on and plan future study, according to Dr. Sangwan. Interactions between elements, such as gut bacteria consuming and producing metabolites, add to the complexity.
 
Dr Sangwan and his team then developed an artificial intelligence (AI) algorithm to combine and analyze the existing studies' datasets and clarify what factors are most relevant for future studies. Surprisingly, Dr Sangwan's analysis revealed that differences in diet (identified through analyzing metabolites) accounted for a significant proportion of the differences observed between the young-onset and older-onset patients.
 
"Researchers - ourselves included - have begun to focus on the gut microbiome as a primary contributor to colon cancer risk. But our data clearly shows that the main driver is diet," Dr. Sangwan says. "We already know the main metabolites associated with young-onset risk, so we can now move our research forward in the correct direction."
 
The team was excited to see diet play such a large role in cancer risk, because it is much easier to identify at-risk patients by counting the metabolites in their blood than it is to sequence the bacterial DNA in their stool for different microbes.
 
"It can actually be very complicated and difficult to change your microbiome," explains Dr. Kamath. "While it's not always easy, it is much simpler to change your diet to prevent colon cancer."
 
Younger colon cancer patients had higher levels of metabolites associated with the production and metabolism of an amino acid called arginine, and with the urea cycle compared to their older peers. These differences may be tied to long-term consumption of red meat and processed meat. The team is now analyzing national datasets to validate their Cleveland Clinic-specific findings in patients across the country.
 
After they show that arginine and urea cycle metabolites (and, by proxy, red and processed meat overconsumption) are elevated across younger adults with colon cancer nationwide, they plan to test whether certain diets or commercially available drugs that regulate arginine production and the urea cycle can help prevent or even treat young-onset colorectal cancer.
 
Dr. Kamath says that even though more research is needed to understand exactly how dietary factors cause colon cancer, his current findings have already changed the way he delivers patient care.
 
"Even though I knew before this study that diet is an important factor in colon cancer risk, I didn't always discuss it with my patients during their first visit. There is so much going on, it can already be so overwhelming," says Dr. Kamath. "Now, I always make sure to bring it up to my 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."