SAN DIEGO—Obese men who suffer from chronic liver disease have an increased risk of developing a common form of liver cancer called hepatocellular carcinoma (HCC), according to a new study published in the journal Cell.
Researchers 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 primary role of TNF is in the regulation of immune cells, but its deregulated production can cause diseases such as rheumatoid arthritis or Crohn’s disease. Ironically, while TNF also was tested for its ability to kill cancer, its chronic production was found to actually enhance tumor development.
IL-6 is known to be involved in the pathogenesis of rheumatoid arthritis, but previous research has shown IL-6 also contributes to the chronic inflammation that leads to liver cancer. Recent epidemiological studies have confirmed the critical role of IL-6 in the progression of viral hepatitis to HCC in humans.
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.
“In addition to HCC, obesity markedly increases the risk of pancreatic, gastrointestinal tract and kidney cancers,” the researchers wrote. “Given the prevalence of obesity in the Western and developing worlds, even a modest increase in cancer risk represents a major public health problem.”