Researchers Build on Diabetes-Liver Cancer Connection

October 30, 2012

Diabetes mellitus is associated with a higher risk of having advanced liver cancer at the time of diagnosis, suggesting that the presence of diabetes may promote more invasive tumor biology, a University of Rochester Medical Center study found.

A number of prior studies have shown various associations between diabetes and cancer in general. The connection makes sense, in part due to the liver’s regulation of sugars, and longtime observations that people prone to liver failure also are prone to diabetes. In addition several prior studies have shown that cancer patients with diabetes often have worse outcomes; the reason for this is not clear.

The recent URMC study adds an important new dimension because it links diabetes to distant metastasis in patients with hepatocellular cancer, a form of liver cancer usually found in people with liver cirrhosis, said corresponding author Gregory C. Connolly, M.D., senior instructor of Medicine at the James P. Wilmot Cancer Center at URMC.

The study was published this month by the journal Cancer Investigation.

“Although our research is preliminary and based on a retrospective dataset, the findings are very interesting and hypothesis-generating,” Connolly said. “The association we detected suggests that patients with liver cancer and diabetes may have changes in cancer cell signaling that promote tumor invasiveness. The more we understand about the mechanisms at work, the more successful we’ll be at treating patients with both diseases.”

Connolly and colleagues looked at disease trends among 265 primary liver cancer patients diagnosed between 1998 and 2008 at Strong Memorial Hospital at URMC.  Of the total, they found that 34 percent had diabetes at the time of the cancer diagnosis. And among the diabetic group, 33 percent had liver cancer that had already spread to distant organs -- compared to 9.7 percent of patients with advanced liver cancer who did not also have diabetes.

Moreover, the diabetic patients who took insulin had the highest rates of advanced cancer, compared to diabetics who managed their blood sugars through diet restriction or oral medications.

In the United States the incidence of diabetes mellitus (high blood sugar) has roughly doubled in the past 20 years; at the same time the rates of hepatocellular carcinoma, the most common form of liver cancer, also rose steadily. Most primary liver cancer is attributed to hepatitis or chronic alcohol abuse, but the National Cancer Institute reported in 2010 that now diabetes is actually associated with a greater percentage of liver cancer cases than any other factor.

Survival rates for advanced liver cancer are dismal. In the URMC study, 85 percent (or 237 people) died during the median follow-up period of 6.5 months. But the patients without diabetes had a median survival time of 7.55 months versus 6.04 months for those who also had diabetes.

“Because the incidence of people with glucose intolerance and liver cirrhosis or primary liver cancer is so strong, it is imperative that we better understand the relationship so that these patients can be treated and managed in the best way possible,” said senior author Aram F. Hezel, M.D., assistant professor of Medicine in Hematology/Oncology at Wilmot.

Connolly is supported by a grant from the James P. Wilmot Research Foundation. Other co-authors are: Alok A. Khorona, M.D., Richard F. Dunne, M.D., and research assistant Afamefuna Nduaguba, of the Department of Medicine; Saman Safadjou, information analyst in the Division of Solid Organ Transplant and Hepatobilary Surgery; and Rui Chen, Ph.D., research assistant professor of Biostatistics.

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