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Soda might fuel an epic video game tournament or a 5-year-old’s manic birthday party, but a startling new study has found that in tumor-prone mice, it drives something else entirely: the growth of colon cancer. Although it’s not clear that humans would react the same way as the rodents, researchers who conducted the new work say their results could help explain a recent rise in colon cancer in young adults—and might even point to ways to treat the disease.
“This is probably the most direct evidence to date that sugar, separate from obesity, can drive the progression of cancer. It’s a model for what happens if you’re predisposed to colon cancer and you chug a can of Coke a day,” says Princeton University biochemist Joshua Rabinowitz, who was not involved with the study.
Sweetened beverage sales took off in the 1980s, when corn subsidies in the United States resulted in cheap, high-fructose corn syrup that flooded the market and replaced table sugar. Since then, our thirst for Big Gulps has been blamed for rising rates of obesity—and, indirectly, cancer. Obesity causes inflammation, thought to help tumors grow. Colon cancer in particular—death rates of which have been on the rise in people under age 50—has been tied to being overweight. But biochemist Lewis Cantley at Weill Cornell Medicine in New York City and his then-postdoc, Jihye Yun, wondered whether there was a more direct link between sweet drinks and cancer.
Together with Weill Cornell postdoc Marcus Goncalves and collaborators, they studied mice that develop colon tumors because they lack a gene, called APC, that has been shown to predispose people to the same cancer when disabled. Each day, the researchers squirted about one-tenth of a teaspoon of water containing 25% high-fructose corn syrup into the animals’ stomachs. That was too little sugar to make the mice gain weight, but it was still the equivalent of almost a can of soda a day.
The sugar imbibers didn’t develop more colon tumors than mice that were given plain water. But after about 2 months, most of the tumors in the sugar-swilling rodents had grown larger and more invasive than the tumors of the control mice, Cantley’s team reports today in Science. Tests with isotope-labeled glucose and fructose—the two components in high-fructose corn syrup—revealed that much of the fructose skipped over its regular route of absorption into the blood through the small intestine and instead went straight to the large intestine, or colon, where tumor cells sucked it up along with glucose.
Once inside the tumor cells, the fructose was broken down by an enzyme called fructokinase (KHK), which lowered the cell’s energy level and triggered more glucose metabolism to restore it. This glycolysis also produced fats needed by the tumor cells to grow, the researchers found. In mice engineered to lack the KHK enzyme as well as APC, tumors grew no larger than in control APC knockout animals that didn’t get corn syrup.
The team says the mouse results suggest sweet beverages—including those containing table sugar (also a fructose and glucose mixture)—could be speeding the growth of precancerous polyps in people who might otherwise take decades to develop cancer. “Even a modest amount of sugary drinks could shorten the time that cancer takes to develop,” says Yun, now an assistant professor at Baylor College of Medicine in Houston, Texas, where her lab helped complete the study.
“The experiments are well done and the results are convincing,” says physiologist Luc Tappy of the University of Lausanne in Switzerland. But he and others caution that it’s not yet clear how relevant the rodent experiments are to people, who may blunt the corn syrup’s effects by drinking sodas slowly or with food. “Is it moderately or mildly increasing the risk? Or is it negligible compared to other factors we’re aware of?” says physician-scientist Mark Herman of Duke University in Durham, North Carolina.
To answer that question, Cantley’s team hopes to study whether a low-sugar diet slows intestinal polyp growth in people genetically predisposed to develop them. They also suggest a KHK-inhibiting drug in clinical trials for fatty liver disease could potentially be added to standard drugs as part of a clinical trial to treat people with colon cancer.
Source: Science Mag