Diabetes, abdominal obesity, weight change, metabolic factors and risk of liver cancer in the European Prospective Investigation into Cancer and Nutrition

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The incidence of hepatocellular carcinoma (HCC), the predominant form of liver cancer, is increasing in Western civilizations. The increasing occurrence of non-alcoholic steatohepatitis (NASH) which largely occurs in obese or diabetic individuals has been hypothesized to largely account for this phenomenon. General obesity and diabetes mellitus have been associated with HCC in some studies. Evidence emerges that it is primarily abdominal fat accumulation which is related to metabolic abnormalities, however, little is known about these factors with respect to HCC incidence. Furthermore, the time period of weight gain and interactions with known HCC risk factors like hepatitis C or B virus infections might be important in disease etiology. We propose to investigate the associations of abdominal obesity, diabetes, weight change and metabolic factors (e.g. interleukin-6, adiponectin, fetuin A) with risk of liver cancer (HCC, cholangiocarcinoma, gallbladder cancer) in the European Prospective Investigation into Cancer Nutrition Study, a multicenter cohort study comprising more than 500,000 study participants. A prospective nested case-control study will be set up including about 300 cases of incident liver cancer and matched controls to address the research questions. This analysis will provide evidence for understanding the role of abdominal obesity, diabetes, weight change, and metabolic factors in the etiology of liver cancer, and promises to be of impact for primary prevention in clinical practice and public health.