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Diet and Disease: Exciting Epigenetics Discoveries at the Nadeau Lab

Recent research in the Nadeau Lab at the Pacific Northwest Research Institute (PNRI), led by Joseph Nadeau, PhD, has provided some surprising answers about the mechanism that leads from a high-fat diet to the development of intestinal cancer. Even more exciting is our new insight into genetic variation — a modifier gene that may be the key to beating this type of cancer.

High-fat Diets Linked to Tumors in Mice

When studying mouse models, the Nadeau Lab and collaborators at University of Pennsylvania, Case Western Reserve University, and other institutions, found that certain types of high-fat diets — specifically corn and coconut-based diets — are associated with increased intestinal tumor formation. This finding intrigued researchers because it very closely resembles familial adenomatous polyposis, a condition that carries a high risk for human colorectal cancer in people who have mutations in a tumor-suppressing gene called Apc.

The first surprising observation in the study was that diet alone played a strong role in cancer development, independent of obesity. “Our results clearly show that eating a high-fat diet is sufficient to increase cancer risk, regardless of obesity,” says Joe.

Additional research revealed that this specific high-fat diet increased production of a pro-inflammatory molecule, C5a. The presence of C5a triggered an immune response meant to destroy foreign invaders that ultimately caused the cancer to develop. However, when mice were given a drug to suppress the activity of the gene responsible for receiving C5a, it prevented the development of intestinal tumors.

Continued study by PNRI’s team and our partners will provide additional insights into how certain high-fat diets play a role in production of the C5a molecule, as well as the potential for immune suppression therapy as a complement to traditional cancer treatments.

Who Is More Likely to Stay Healthy?

Say you have the Apc gene mutation, and you have managed to beat the odds and meet your exact genetic match. Will you both develop cancer? Or could one of you remain healthy? Thanks to this study, we can now say for certain that your diet has a direct impact on whether or not you will develop cancer. Fortunately, we are quickly learning more about how to keep you and your hypothetical twin healthy — even if you have a genetic predisposition to disease.

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