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Type 2 diabetes raises cancer risk

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People with type 2 diabetes might be at somewhat higher risk of developing liver cancer, according to a large, long-term study.

The research suggests that those with type 2 diabetes have about two to three times greater risk of developing hepatocellular carcinoma (HCC) - the most common type of liver cancer - compared to those without diabetes. Still, the risk of developing liver cancer remains low, experts said.

Race and ethnicity might also play a role in increasing the odds of liver cancer, the researchers said.

How the study was done

An estimated 26% of liver cancer cases in Latino study participants and 20% of cases in Hawaiians were attributed to diabetes. Among blacks and Japanese-Americans, the researchers estimated 13% and 12% of cases, respectively, were attributed to diabetes. Among whites, the rate was 6%.

"In general, if you're a [type 2] diabetic, you're at greater risk of liver cancer," said lead author V. Wendy Setiawan, an assistant professor at the Keck School of Medicine at the University of Southern California.

Yet the actual risk of liver cancer -- even for those with type 2 diabetes -- is still extraordinarily low, said Dr. David Bernstein, chief of hepatology at North Shore University Hospital in Manhasset, N.Y.

Although liver cancer is relatively rare, it has been on the rise worldwide and often is associated with viral hepatitis infections and liver diseases, such as cirrhosis.

New cases of HCC in the United States have tripled in the past 30 years, with Latinos and blacks experiencing the largest increase, Setiawan said. During that time, type 2 diabetes also has become increasingly common.

What might the connection be?

It's possible that the increased risk of liver cancer could be associated with the medications people with diabetes take to control their blood sugar, said Dr. James D'Olimpio, an oncologist at Monter Cancer Center in Lake Success, N.Y. "Some medications are known to inhibit normal suppression of cancer," he said.

"Some of the drugs already have [U.S. Food and Drug Administration-ordered] black box warnings for bladder cancer," D'Olimpio said. "It's not a stretch to think there might be other relationships between diabetes drugs and pancreatic or liver cancer. Diabetes is already associated with a high risk of developing pancreatic cancer."

People with type 2 diabetes often develop a condition called "fatty liver," D'Olimpio said. In these cases, the liver has trouble handling the abundance of fat in its cells and gradually becomes inflamed. That situation can trigger a cascade of problems, including cirrhosis (a chronic disease of the liver), fibrosis (thickening and scaring of tissue) and, ultimately, cancer, he said.

D'Olimpio said fatty liver disease is the No. 1 cause of HCC. "[Type 2] diabetics have twice the chance of having a fatty liver, at least," he said. "If you're an African-American or Latino, that may make you even more susceptible."

People with type 1 diabetes, however, do not have an increased risk of liver cancer, he said.

No cause-and-effect shown

The study analyzed data collected between 1993 and 1996 from nearly 170,000 black, Native Hawaiian, Japanese-American, Latino and white adults. Researchers followed up with the participants about 16 years after they had answered a comprehensive health questionnaire. Over that time, about 500 participants had developed liver cancer.

Information about risk factors -- such as age, whether they had type 2 diabetes, alcohol intake, body-mass index (a measure of body fat) and cigarette smoking -- was analyzed, and blood tests for hepatitis B and hepatitis C were performed on about 700 of the participants, with and without liver cancer.

Whether people smoked or drank alcohol did not appear to change the relationship between having diabetes and getting liver cancer, the researchers said.

Although the study found an association between having type 2 diabetes and developing liver cancer, it did not prove a cause-and-effect relationship.

North Shore's Bernstein urged caution in interpreting the results. "It's a single study that talks about a large number of people with a common disease like diabetes and links it to liver cancer," he said. "We have a lot more learning to do and more work is needed to prove an association and define what the risk really is."

A study this month by the American Diabetes Association showed that many Americans are unaware that they are at risk for type 2 diabetes. D'Olimpio urged people to get the simple blood test, called fasting blood sugar, to test for diabetes.

The next step is to learn what role genetics may play in whether an individual with type 2 diabetes will develop liver cancer, study author Setiawan said.

More information

Learn more about liver cancer from the U.S. National Library of Medicine.

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