Red Meat and Cancer: Has a Mechanism Been Uncovered?

Nick Mulcahy

January 02, 2015

The long-term consumption of red meat has repeatedly been associated with a higher risk for certain cancers in humans, particularly colorectal cancer.

Now researchers at the University of California (UC), San Diego, have evidence that a specific type of sugar found in red meat may promote inflammation and cancer progression.

However, their study is in mice, and their results may be hard to demonstrate in humans, they acknowledge in an article published online December 29 in the Proceedings of the National Academy of Sciences.

The focus of the research is a sugar known as nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc), which is naturally found in most mammals but not in humans. It occurs in varieties of meat, especially beef, pork, and lamb, that humans often consume.

In this study, the researchers hypothesized that eating red meat could lead to inflammation ― if the human body's immune system is constantly generating antibodies against consumed animal Neu5Gc, a foreign molecule.

To test this hypothesis, the team needed an animal model that was similar to humans insofar as the animal would, like humans, not have Neu5Gc itself.

They managed to create that by genetically engineering mice that lacked Neu5Gc and thus produced antibodies against it, mimicking the situation in humans.

When these genetically engineered mice were fed Neu5Gc, they developed systemic inflammation, with a fivefold increase in spontaneous tumor formation in the liver and Neu5Gc accumulation in the tumors. The researchers explained that such mice are prone to liver tumors, which could account for why the malignancies showed up there.

"This is the first time we have directly shown that mimicking the exact situation in humans ― feeding nonhuman Neu5Gc and inducing anti-Neu5Gc antibodies ― increases spontaneous cancers in mice," said lead author Ajit Varki, MD, of the UC San Diego Moores Cancer Center, in a press statement.

"Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups," he added.

"The final proof in humans will be much harder to come by," Dr Varki also said.

However, he also said that the new findings may help explain potential connections between red meat consumption and other diseases exacerbated by chronic inflammation, such as atherosclerosis and type 2 diabetes.

The new research adds to a substantial body of literature about red meat consumption and cancer risk.

However, the association between the two has never been definitively proven. The weaknesses of the evidence are manifold, as noted in an article published in 2013 by Medscape Medical News.

The research was funded by the Ellison Medical Foundation, the National Cancer Institute, a Samuel and Ruth Engelberg fellowship from the Cancer Research Institute, and a Swiss National Science Foundation fellowship. Dr Ajit Varki and a colleague are cofounders and have equity interest in SiaMab Therapeutics, Inc, a biotech company with an interest in Neu5Gc and anti-Neu5Gc antibodies.

Proc Natl Acad Sci. Published online December 29, 2014. Abstract

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