How Lifestyle and Gut Health May Influence Early-Onset Colorectal Cancer

New findings published in the American Association for Cancer Research journal Cancer Research Communications highlight potential biological differences in early-onset colorectal cancer. These insights suggest that environmental and lifestyle factors may play a more significant role than previously recognized, offering new opportunities for prevention and early detection.

Dr. Ning Jin, a physician, sat down with CURE to discuss the study’s key findings and their implications for patients. In this interview, she explores how epigenetic changes and microbial-immune interactions may contribute to early-onset colorectal cancer.

Jin also serves as an associate professor of medical oncology, Department of Internal Medicine, the Ohio State University Comprehensive Cancer Center, The James Gastrointestinal and Colorectal Cancer Center.

CURE: Could you briefly summarize the key findings of your recent study on early-onset colorectal cancer in young adults?

Jin: Our study reveals that early-onset colorectal cancer tumors exhibit signs of accelerated epigenetic aging, with a DNA methylation age approximately 12 years older than average-onset colorectal cancer tumors. We identified specific pathways that are related to methylation and gene transcription in early-onset colorectal cancer, including CREB signaling, G protein-coupled receptor (GPCR) signaling, phagosome formation, and S100 family signaling.

While the study found no consistent differences in the specific types or abundance of intratumoral microbes between early-onset colorectal cancer and average-onset colorectal cancer, it discovered that the microbes present in early-onset colorectal cancer tumors (such as Fusobacterium) have significantly stronger correlations with immune cells like neutrophils and activated mast cells. Ultimately, these findings suggest that early-onset colorectal cancer tumors have a heightened, dysregulated immune response to microbes, leading to a state of chronic inflammation that drives tissue aging and premature cancer development.

How do the interactions between the tumor microbiome and the immune system differ in younger patients compared with older patients?

In younger patients (with early-onset colorectal cancer), the interactions between the tumor microbiome and the immune system are significantly stronger and broader than in older patients (average-onset colorectal cancer).

Your study mentions accelerated cellular aging and altered gene activity in tumors of younger adults. What might be driving these changes if not inherited genetic mutations?

The accelerated cellular aging and altered gene activity in early-onset colorectal cancer, when not caused by inherited mutations, are primarily driven by environmental exposures and lifestyle changes. Factors such as a Western diet (high in animal protein/fat and low in fiber), smoking, obesity, physical inactivity and ultra-processed food.

How could these findings influence approaches to prevention or early detection of colorectal cancer in young adults?

First, our study emphasized lifestyle and dietary interventions. Because sporadic early-onset colorectal cancer is strongly linked to environmental factors and intestinal dysbiosis, modifying lifestyle risk factors is a key prevention strategy. Interventions could focus on reducing Western diet habits (which are high in fat and animal protein) and promoting diets rich in fiber and essential nutrients found in green leafy vegetables.

Second, our study notes that DNA methylation changes may be the earliest alterations to occur during the transformation from a benign polyp to cancer. Utilizing the unique epigenetic signatures identified in this research could provide novel biomarkers for early detection.

Are there specific microbes or microbial patterns that appear to play a particularly important role in tumor behavior or immune response?

Regarding broader microbial patterns, the study revealed that the actual abundance or presence of specific microbes does not consistently differ between younger and older patients. Instead, the most important pattern is how the tumor microbiome interacts with the immune system.

Do you see potential for microbiome-targeted therapies as part of treatment for early-onset colorectal cancer?

Viewing "food as medicine" represents a highly promising, microbiome-targeted strategy for cancer prevention, as dietary choices directly dictate the composition and function of our gut bacteria. By shifting away from a Western diet to a Mediterranean diet, individuals can prevent the "intestinal dysbiosis" that triggers tumor-promoting inflammation.

Beyond balancing the microbiome, our food choices actively influence gene expression via epigenetic changes. For instance, when gut microbes break down dietary fiber, they generate short-chain fatty acids like butyrate, which can directly inhibit the abnormal proliferation of colon cells. Consuming vital nutrients may block the inappropriate activation of cancer-causing genes.

Ultimately, intentional dietary modifications provide a natural defense mechanism to sustain microbial harmony and slow down the aging process in early-onset colorectal cancer.

What do you think is the most important takeaway for patients from this research?

The most important takeaway for patients is that the development of sporadic early-onset colorectal cancer is largely driven by modifiable environmental and lifestyle factors, rather than just inherited genetics. Because the study reveals that tumors in young adults exhibit accelerated epigenetic aging, everyday choices like healthy diet become a critical line of defense.

Transcript has been edited for clarity and conciseness.

References

1. “Epigenetic Modulation, Intratumoral Microbiome, and Immunity in Early-Onset Colorectal Cancer,” by Ning Jin. Cancer Research Communications.

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