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Campus Currents May 2007: Volume 4, Number 2

Obesity and Cancer

Excess body weight can increase the risk of all cancers—1.5-fold in men and 1.6-fold in women.

Researchers at UC San Diego’s School of Medicine have conclusively demonstrated that obesity is tumor-promoting and have ­obtained evidence that this effect depends on induction of low-grade, chronic inflammation.

Their results, published in the journal Cell, may suggest a novel therapy to prevent the development of Hepatocellular Carcinoma (HCC) in obese men who suffer from chronic liver disease.

Michael Karin, Ph.D., distinguished professor of Pharmacology in UCSD’s Laboratory of Gene Regulation and Signal Transduction, led the study, which found that obesity enhanced the development of HCC by stimulating the production of tumor-promoting cyto­kines—interleukin-6 (Il-6) and tumor necrosis factor (TNF)—that also cause chronic inflammation. Production of these signaling molecules, which are elevated in obese mice and in humans, causes inflammation of the liver and activation of a tumor-promoting transcription factor, a protein called STAT3. This protein in turn activates the formation and growth of liver cancer.

The actual increase in cancer risk is dependent on the type of cancer and the body-mass-index (BMI). The largest effect of BMI higher than 25 (the recommended BMI level) is seen on HCC; the risk of this type of liver cancer is increased by up to 4.5-fold in men with a BMI of between 35 and 40. But the effect of excess body weight increases the risk of all cancers—1.5-fold in men and 1.6-fold in women, according to Karin.

“In addition to HCC, obesity markedly increases the risk of pancreatic, gastrointestinal tract and kidney cancers,” Karin says.  “Given the prevalence of obesity in the Western and developing worlds, even a modest increase in cancer risk represents a major public health problem.”

The new UCSD research suggests that anti-TNF drugs, currently used in the treatment of chronic inflammatory diseases, may be used to prevent HCC development in obese men who suffer from chronic liver disease. According to the studies in mice, inhibition of TNF signaling may even prevent hepatosteatosis, or accumulation of fat in the
liver.

Debra Kain