Diabetes is the Most Common Risk Factor for Liver Cancer in the U.S.

Drawing of the inside of a body showing the liver, colon and lungs.

The incidence of hepatocellular carcinoma (HCC), the most common type of primary liver cancer, has been increasing in the United States for several decades. Prior estimates suggested that only about 40 percent of HCC was associated with known risk factors in the U.S., however. To obtain a better estimate scientists from NCI examined the association of HCC with hepatitis B virus, hepatitis C virus, alcohol-related liver disease, diabetes, obesity and several rare metabolic disorders. They found that diabetes was associated with a greater percentage of HCC cases than any other factor.

“Although our analyses found chronic [hepatitis C virus] infection conferred the highest risk of HCC in an individual, diabetes was associated with the largest proportion of HCC in the population. In theory, eliminating diabetes from the population would result in a greater reduction in HCC incidence than the elimination of any other single factor,” said study leader Katherine A. McGlynn, Ph.D., M.P.H., senior investigator, Division of Cancer Epidemiology and Genetics.

To conduct their research, McGlynn and her team analyzed data from the SEER-Medicare linked database.  NCI’s Surveillance, Epidemiology and End Results (SEER) program collects cancer incidence and survival data from population-based registries that cover approximately 26 percent of the U.S. population. The SEER-Medicare database links medical diagnoses in the Medicare population to cancer diagnoses in the SEER population. The case population for the HCC study consisted of 5,607 people diagnosed with HCC between 1994 and 2005. Cases had at least three years of Medicare coverage before their cancer diagnosis. The control population was drawn from a random sample of Medicare recipients residing within SEER catchment areas. Overall, approximately 63 percent of HCC was associated with one or more of the risk factors mentioned above. Diabetes was associated with the greatest percentage of cases (34 percent), followed by alcohol-related disorders (24 percent), hepatitis C virus infection (21 percent), hepatitis B virus infection (6 percent), rare metabolic disorders (3 percent) and obesity (3 percent).  These factors account for greater percentage of HCC in males, 65 percent versus 61 percent in females. They were also more strongly linked to HCC in certain racial or ethnic sub-groups, 68 percent of HCC in Asians compared to only 53 percent in African-Americans.

Symptoms of Liver Cancer

  • Pain in the upper abdomen on the right side
  • A lump or a feeling of heaviness in the upper abdomen
  • Swollen abdomen (bloating)
  • Loss of appetite and feelings of fullness
  • Weight loss
  • Weakness or feeling very tired
  • Nausea and vomiting
  • Yellow skin and eyes, pale stools, and dark urine from jaundice
  • Fever

To learn more about liver cancer visit the NCI’s Liver Cancer page.

To examine trends over time, the researchers compared data from 1994 to 1999 with data from 2000 to 2005.  Between the two time periods, the total proportion of HCC explained by the risk factors increased from 55 percent to 65 percent. No single factor was responsible for the increase in attributable risk over time. The researchers also noted that, although the proportion of cancer explained by known factors increased to 65 percent, over one-third of HCC cases remain unexplained.

The researchers are currently expanding on these results with additional studies to determine whether the risk of HCC among people with diabetes is affected by other factors, including diabetes medications and obesity.

McGlynn will present the finding of this work, Attributable Risks for Hepatocellular Carcinoma in the United States, at the 101st Annual Meeting of the American Association for Cancer Research (AACR).

Early liver cancer often doesn’t cause symptoms. When the cancer grows larger, people may notice one or more of these common symptoms:

These symptoms may be caused by liver cancer or other health problems. If you have any of these symptoms, you should tell your doctor so that problems can be diagnosed and treated as early as possible. To learn more see NCI’s publication What You Need to Know About Liver Cancer.

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