Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X4, Canada; email:
Annu Rev Med. 2015;66:281-96. doi: 10.1146/annurev-med-051613-012328. Epub 2014 Nov 12.
There is growing appreciation that the current obesity epidemic is associated with increases in cancer incidence at a population level and may lead to poor cancer outcomes; concurrent decreases in cancer mortality at a population level may represent a paradox, i.e., they may also reflect improvements in the diagnosis and treatment of cancer that mask obesity effects. An association of obesity with cancer is biologically plausible because adipose tissue is biologically active, secreting estrogens, adipokines, and cytokines. In obesity, adipose tissue reprogramming may lead to insulin resistance, with or without diabetes, and it may contribute to cancer growth and progression locally or through systemic effects. Obesity-associated changes impact cancer in a complex fashion, potentially acting directly on cells through pathways, such as the phosphoinositide 3-kinase (PI3K) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways, or indirectly via changes in the tumor microenvironment. Approaches to obesity management are discussed, and the potential for pharmacologic interventions that target the obesity-cancer link is addressed.
人们越来越认识到，当前的肥胖症流行与人群中癌症发病率的增加有关，并且可能导致癌症预后不良；同时，人群中癌症死亡率的下降可能代表一种悖论，即这也可能反映了癌症诊断和治疗的改善，掩盖了肥胖的影响。肥胖与癌症之间存在关联具有生物学合理性，因为脂肪组织具有生物活性，可分泌雌激素、脂肪因子和细胞因子。在肥胖中，脂肪组织的重新编程可能导致胰岛素抵抗，无论是否存在糖尿病，并且它可能通过局部或全身作用促进癌症的生长和进展。肥胖相关的变化以复杂的方式影响癌症，可能通过途径直接作用于细胞，例如磷酸肌醇 3-激酶 (PI3K) 和 Janus 激酶-信号转导和转录激活因子 (JAK-STAT) 途径，或通过肿瘤微环境的变化间接作用。讨论了肥胖症的管理方法，并探讨了针对肥胖症与癌症之间联系的药物干预的可能性。
