Metabolic Syndrome Identified as Risk Factor for Liver Cancer

Roxanne Nelson

April 05, 2011

April 5, 2011 (Orlando, Florida) — Metabolic syndrome is a known risk factor for diabetes and heart disease, but researchers now report that it might also place individuals at higher risk for the development of liver cancer.

According to data presented here at the American Association for Cancer Research 102nd Annual Meeting, metabolic syndrome is associated with an increased risk of developing hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

The authors found that 37.1% of patients with hepatocellular carcinoma and 29.7% with intrahepatic carcinoma had preexisting metabolic syndrome. Conversely, only 17.1% of individuals without cancer had metabolic syndrome.

Dr. Lewis Roberts

"Given the high and increasing rates of obesity, the metabolic syndrome, and nonalcoholic fatty liver disease in the United States, this is a very important and timely study," said Lewis Roberts, PhD, who was approached by Medscape Medical News for independent comment. "It shows that the rates of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma are higher in individuals with the metabolic syndrome."

"It is important for physicians and other healthcare workers to be aware of these associations, as people with metabolic syndrome are not generally viewed as being at high risk for these cancers," explained Dr. Roberts, professor of medicine at the Mayo Clinic in Rochester, Minnesota.

Although the specific mechanism linking these 2 conditions is still undefined, Dr. Roberts pointed out that metabolic syndrome is associated with increased inflammation in the liver and other tissues. "Inflammation is an important cause of cell injury and genetic damage to cells; this is a potential link between the metabolic syndrome and both hepatocellular carcinoma and intrahepatic cholangiocarcinoma," he said.

There is an urgent need for more research in this area to further our understanding of the specific mechanisms that drive cancer development in individuals with metabolic syndrome and to determine whether there are low-risk methods that can be used to prevent cancer development, he added.

Incidence Rising in the United States

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are the 2 most common histologic types of primary liver cancer.

"In the United States, hepatocellular carcinoma is by far the most common, and accounts for about 70% of all primary liver cancers, whereas intrahepatic cholangiocarcinoma accounts for about 17%," said lead author Katherine McGlynn, PhD, a senior investigator at the National Cancer Institute.

Dr. McGlynn also noted that liver cancers are far more common among racial/ethnic minorities in the United States, especially hepatocellular carcinoma. Compared with white Americans, the incidence among all racial/ethnic minorities is at least 2-fold higher. The incidence of both types of cancer is rising; since the early 1970s, the incidence of hepatocellular carcinoma has jumped 212%, and the incidence of intrahepatic cholangiocarcinoma has risen by about 85%.

Metabolic syndrome, which is a collection of symptoms characterized by increased fasting glucose level, central adiposity, dyslipoproteinemia, and hypertension, has been previously linked to hepatocellular carcinoma, she explained, but the magnitude of the association has not been investigated at the population level in the United States.

"By the early years of the 21st century, unfortunately, over a third of the population is thought to have metabolic syndrome," she said. "Unfortunately, the prevalence is higher in some racial/ethnic minorities. Mexican Americans have a prevalence of about 45%."

Significantly More Common

Dr. McGlynn and colleagues used the Surveillance, Epidemiology, and End Results Program (SEER)–Medicare linked database to identify all people 65 years and older who were diagnosed with histologically confirmed hepatocellular carcinoma and intrahepatic cholangiocarcinoma between 1993 and 2005.

A total of 3,649 hepatocellular carcinoma cases and 743 intrahepatic cholangiocarcinoma cases were identified, as were 195,953 individuals without cancer who met the study inclusion criteria.

The team found that metabolic syndrome was significantly more common among people who developed liver cancer. After adjustment for demographic features and other risk factors, metabolic syndrome remained significantly associated with an increased risk for hepatocellular carcinoma (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.96 to 2.31; P < .0001) and intrahepatic cholangiocarcinoma (OR, 1.56; 95% CI, 1.32 to 1.83; P < .0001).

Interventions Needed

As obesity rates continue to rise in the United States, so will the incidence of metabolic syndrome. Better interventions/methods are needed for initiating changes in diet and lifestyle, Dr. Roberts said.

Experts in the liver cancer field are very concerned that as efforts to limit the spread of hepatitis C and hepatitis B, currently the most common causes of liver cancer in the United States, are more and more successful, the metabolic syndrome and fatty liver disease will become the predominant causes of an increasing epidemic of liver and biliary cancers," he said.

"It is critical to initiate and support the necessary dietary and lifestyle interventions for preventing the development of metabolic syndrome, particularly in children and young adults," Dr. Roberts added.

American Association for Cancer Research (AACR) 102nd Annual Meeting: Abstract 945. Presented April 3, 2011.

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