Liver Cancer Linked to Metabolic Syndrome

Roxanne Nelson

July 28, 2011

July 28, 2011 — Metabolic syndrome, the cluster of risk factors that increase the risk for cardiovascular disease and diabetes, appears to be linked to liver cancer.

The results of a large population-based study found that metabolic syndrome was associated with an increased risk of developing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

The study authors found that metabolic syndrome was significantly more common in individuals who developed HCC (37.1%) and ICC (29.7%) than in a comparison group (17.1%; P < .0001). Even after multiple logistic regression analyses, metabolic syndrome remained significantly associated with an increased risk for both HCC (odds ratio, 2.13; P < .0001) and ICC (odds ratio, 1.56; P < .0001).

The data, which were initially presented in April at the American Association for Cancer Research (AACR) annual meeting, appear in the August issue of Hepatology.

"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," Lewis Roberts, PhD, told Medscape Medical News during the AACR meeting. "It shows that the rates of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma are higher in individuals with the metabolic syndrome."

Dr. Roberts, professor of medicine at the Mayo Clinic in Rochester, Minnesota, who was not involved in the liver cancer study, pointed out that 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."

Rising Rates Not Fully Explained

Incidence rates of both HCC and ICC have been rising in the United States. Chronic infection with hepatitis C virus and hepatitis B virus and excessive alcohol consumption are recognized risk factors for HCC in industrialized nations, but they do not fully explain the rising incidence, the authors point out. Between 20% and 50% of all cases are idiopathic.

Similarly, even though ICC has been associated with a number of diseases of the biliary tract or liver, these factors only account for a small proportion of the attributable risk for ICC in the United States, according to the authors. Many cases of ICC appear to be unrelated to any of the known risk factors.

Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis have both been associated with metabolic syndrome. The authors point out that in conjunction with the recent worldwide epidemic of obesity and metabolic syndrome, the incidence and prevalence of nonalcoholic fatty liver disease has increased.

The association between metabolic syndrome and HCC has been documented in case reports, case series, and longitudinal studies, but there is a lack of larger population-based studies. In addition, studies investigating the possible impact of metabolic syndrome on ICC risk are very limited.

Significant Association Observed

In their study, Tania M. Welzel, MD, MHS, from the division of cancer epidemiology and genetics at the National Cancer Institute, in Rockville, Maryland, and colleagues investigated the association between metabolic syndrome and liver cancer using the Surveillance, Epidemiology, and End Results (SEER)–Medicare databases, which link cancer registry data and Medicare enrollment and claims files.

The authors identified all individuals 65 years and older who were diagnosed with HCC or ICC between 1994 and 2005. Overall, there were 16,448 cases of HCC and 3,005 cases of ICC; of those, 3,649 cases of HCC and 743 cases of ICC met the inclusion criteria.

The individual conditions of metabolic syndrome, including impaired fasting glucose/diabetes, dyslipoproteinemia, hypertension, and obesity, were each significantly associated with the development of HCC (P < .0001). When combined, metabolic syndrome was significantly associated with HCC (37.1% vs 17.1%; P < .0001).

Similarly, the individual components of metabolic syndrome were each significantly more common in the ICC group than in the control group (P < .0005). Thus, metabolic syndrome was also significantly associated with the development of ICC (29.7% vs 17.1%; P < .0001).

Within this cohort, 42.9% of the patients with HCC and 43.3% of the patients with ICC had no history of any previously established risk factor (excluding metabolic conditions). Among those with idiopathic disease, metabolic syndrome was present in 15.7% of the patients with HCC and 11.6% of the patients with ICC.

The authors have disclosed no relevant financial relationships.

Hepatology. 2011;54:463-471. Abstract

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