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

肝癌的主要形式肝细胞癌（HCC）的发病率在西方文明中正在增加。非酒精性脂肪性肝炎（NASH）的发生率越来越高，主要发生在肥胖或糖尿病个体中，已被假设为主要原因。在一些研究中，一般肥胖和糖尿病与HCC相关。有证据表明，它主要是腹部脂肪堆积，这是与代谢异常，然而，鲜为人知的是，这些因素与肝癌的发病率。此外，体重增加的时间段和与已知的HCC危险因素如丙型肝炎或B病毒感染的相互作用可能在疾病病因学中很重要。我们建议在欧洲癌症营养前瞻性研究中调查腹部肥胖、糖尿病、体重变化和代谢因素（如白细胞介素-6、脂联素、胎球蛋白A）与肝癌（HCC、胆管癌、胆囊癌）风险的相关性，这是一项多中心队列研究，包括超过50万名研究参与者。将建立一项前瞻性巢式病例对照研究，包括约300例肝癌病例和匹配的对照，以解决研究问题。该分析将为了解腹型肥胖、糖尿病、体重变化和代谢因素在肝癌病因中的作用提供证据，并有望对临床实践和公共卫生的一级预防产生影响。

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.