Aleksandrova Krasimira, Stelmach-Mardas Marta, Schlesinger Sabrina
Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
Recent Results Cancer Res. 2016;208:177-198. doi: 10.1007/978-3-319-42542-9_10.
Obesity and related metabolic disorders have become globally prevalent posing a challenge for the chronically damaged liver and predisposing the development and progression of cancer. The rising phenomenon of "obesity epidemic" may provide means for understanding why liver cancer is one of the few malignancies with rising incidence in developed countries over the last decades. Non-alcoholic fatty liver disease associated with obesity, insulin resistance, and type 2 diabetes is an increasingly recognized trigger for liver cancer in Western populations characterized by low prevalence of established risk factors for liver cancer such as viral hepatitis and hepatotoxin exposure. Accumulating evidence has established an association between higher body mass index as an indicator of general obesity and higher risk of primary liver cancer. The associations are stronger in men, in patients with underlying liver disease and in white ethnic groups. Abdominal obesity, weight gain in adult life and metabolic factors related to visceral fat accumulation were also suggested as important risk factors for liver cancer; however, more studies are needed to evaluate these associations. The association of obesity and metabolic parameters with liver cancer survival remains controversial. It is unclear which exact mechanisms could provide links between obesity and liver cancer risk. Recent evidence has implicated several molecular pathways in obesity-associated liver cancer. These include insulin resistance leading to increased levels of insulin and insulin-like growth factors, chronic inflammation, adipose tissue remodeling, pro-inflammatory cytokine and adipokine secretion, and altered gut microbiota. These mechanisms coincide with inflammatory and metabolic processes occurring in non-alcoholic fatty liver disease predisposing cancer development and progression. In the context of the current evidence, better understanding of the role of obesity and related metabolic factors may help in improving current strategies for liver cancer prevention.
肥胖及相关代谢紊乱在全球范围内普遍存在，对长期受损的肝脏构成挑战，并易引发癌症的发生和发展。“肥胖流行”这一日益凸显的现象或许能为理解为何肝癌是过去几十年来发达国家中少数发病率呈上升趋势的恶性肿瘤之一提供线索。与肥胖、胰岛素抵抗及2型糖尿病相关的非酒精性脂肪性肝病，在以肝癌既定危险因素（如病毒性肝炎和接触肝毒素）低流行率为特征的西方人群中，正日益被视为肝癌的一个触发因素。越来越多的证据表明，作为一般肥胖指标的较高体重指数与原发性肝癌的较高风险之间存在关联。这种关联在男性、患有潜在肝病的患者以及白人种族群体中更为明显。腹部肥胖、成年期体重增加以及与内脏脂肪堆积相关的代谢因素也被认为是肝癌的重要危险因素；然而，需要更多研究来评估这些关联。肥胖及代谢参数与肝癌生存率之间的关联仍存在争议。目前尚不清楚究竟哪些确切机制能在肥胖与肝癌风险之间建立联系。最近的证据表明，肥胖相关肝癌涉及多种分子途径。这些途径包括胰岛素抵抗导致胰岛素和胰岛素样生长因子水平升高、慢性炎症、脂肪组织重塑、促炎细胞因子和脂肪因子分泌以及肠道微生物群改变。这些机制与非酒精性脂肪性肝病中发生的炎症和代谢过程相吻合，易引发癌症的发生和发展。基于当前证据，更好地理解肥胖及相关代谢因素的作用可能有助于改进当前的肝癌预防策略。
