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

在西方文明中，作为肝癌的主要形式，肝细胞癌的发病率正在上升。非酒精性脂肪性肝炎(NASH)的发病率增加，主要发生在肥胖或糖尿病患者中，已被假设为这一现象的主要原因。在一些研究中，一般肥胖和糖尿病与肝细胞癌有关。有证据表明，主要是腹部脂肪堆积与代谢异常有关，然而，关于这些因素与肝癌发病的关系却知之甚少。此外，体重增加的时间段以及与已知的肝细胞癌危险因素(如丙型肝炎或乙肝病毒感染)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调查研究中调查腹型肥胖、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(肝癌、胆管癌、胆囊癌)风险的关系，这是一项由50多万名研究参与者组成的多中心队列研究。将建立一项前瞻性嵌套病例对照研究，包括大约300例发生肝癌的病例和配对对照，以解决研究问题。这一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.