ISLAMABAD: Does sugar, which makes all things delicious, lead to cancer?

A biologic mechanism in yeast cells may explain the relationship between sugar and malignant tumors, according to a recent study published in the journal Nature Communications.

The nine-year research project may even influence personal medicine and diets for cancer patients, the authors concluded. The study begins by looking closely at cancer cells' appetite for sugar.

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Scientists understand that cancer cells support their rapid reproduction by rewiring their metabolisms to take glucose, ferment it and produce lactate.

Conversely, healthy cells continue with normal respiration, a process in which they take glucose and break it down into carbon dioxide and water.

This "switch of cancer cells from respiration to fermentation is something that was discovered by Otto Warburg, a German biochemist, about 70 or 80 years ago," said microbiologist Johan M. Thevelein, senior author of the study and a professor at KU Leuven in Belgium. It is known as "the Warburg effect."

Fermentation of sugar to lactic acid produces about 15 times less energy than respiration of sugar, Thevelein noted. Yet cancer cells "grow much more rapidly than normal cells, and yeast actually grows the fastest when they ferment," he noted.
"This is weird," he said, and it raises an important question: Is the Warburg effect a symptom of cancer -- or a cause of it?

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Searching for the answer, Thevelein and his colleagues experimented with yeast cells since, just like cancer cells, they are known to favor fermentation over respiration.
The researchers found an intermediate compound that is a "potent activator" of the RAS protein. RAS is a proto-oncogene: a gene that codes for proteins that help to regulate cell growth and differentiation. Proto-oncogenes can become oncogenes or cancer-causing genes when mutations occur. Mutant forms of RAS proteins are present in many tumors, Thevelein said.

The new study, then, reveals "a vicious cycle," he said.

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As sugar is broken down in cells, the intermediate compound activates the RAS proteins, and this in turn stimulates cell proliferation, he said.

This cycle seen in yeast cells might help explain the aggressiveness of cancer.
"Very interesting," said Dr. Jennifer Ligibel, chairwoman of the American Society of Clinical Oncology's energy balance committee. Still, she urges caution in interpreting these findings.

"It's important to not make too many jumps into a patient message based on a study of yeast," she said.

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Even though the researchers pinpointed some similarities between yeast and human cancer cells, Ligibel explained, "it's important to recognize we're a few steps away from even human cancer cells in a test tube."

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The study showed only an increased rate of cell growth triggered by glucose, she said. Even though the team showed RAS pathways being activated, this "actually didn't result in the cells replicating more quickly," she said.

Still, the data are "incredible," said Ligibel, who is also an associate professor of medicine at Harvard Medical School. "This is really one of the first studies that's provided a biologic mechanism that could explain a relationship between glucose itself and cancer progression.

"When we think about the relationship between sugar and cancer -- when we think about what drives the level of sugar in someone's body -- it's primarily related to their weight," Ligibel said.

When people are heavier, their bodies manage sugar differently than those of people who are lighter. This sugar management is what leads to type 2 diabetes, a disease in which blood sugar is high and levels of insulin, the hormone the body uses to manage blood sugar, begins to rise because the body becomes resistant to its effects.

"We've known for a while that having a higher blood sugar and having a higher level of insulin in your system are both linked to the risk of developing cancer," Ligibel said.