Nimptsch Katharina, Pischon Tobias
Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Recent Results Cancer Res. 2016;208:199-217. doi: 10.1007/978-3-319-42542-9_11.
Obesity is associated with metabolic alterations that may pose a biological link between body fatness and risk of cancer. Elucidating the role of obesity-related biomarkers in cancer development is essential for developing targeted strategies aiming at obesity-associated cancer prevention. Molecular epidemiological studies of the past decades have provided evidence that major hormonal pathways linking obesity and cancer risk include the insulin and insulin-like growth factor-1 (IGF-1) axis, sex-steroid hormones, adipokines and chronic low-grade inflammation. These pathways are interrelated with each other, and their importance varies by obesity-related cancer type. The insulin/IGF-1 axis has been implicated to play an important mediating role in the association between obesity and risk of pancreatic, colorectal and prostate cancer. Endogenous sex-steroid hormone concentrations, in particular obesity-associated pre-diagnostic elevations of estrogens and androgens, play an important role in postmenopausal breast cancer and endometrial cancer development. The adipokines adiponectin and leptin and adipocyte-mediated chronic low-grade inflammation represented by the acute-phase C-reactive protein may explain a substantial part of the association between obesity and risk of colorectal cancer. There is less evidence on whether these hormonal pathways play a mediating role in other obesity-associated types of cancer. In this chapter, the molecular epidemiologic evidence from prospective studies relating circulating obesity-related biomarkers to cancer risk is summarized, taking into account available evidence from Mendelian Randomization investigations aiming at improving causal inference.
肥胖与代谢改变相关，而代谢改变可能在体脂与癌症风险之间构成生物学联系。阐明肥胖相关生物标志物在癌症发生中的作用对于制定旨在预防肥胖相关癌症的靶向策略至关重要。过去几十年的分子流行病学研究提供了证据，表明连接肥胖与癌症风险的主要激素途径包括胰岛素和胰岛素样生长因子-1（IGF-1）轴、性类固醇激素、脂肪因子和慢性低度炎症。这些途径相互关联，其重要性因肥胖相关癌症类型而异。胰岛素/IGF-1轴在肥胖与胰腺癌、结直肠癌和前列腺癌风险之间的关联中被认为起重要中介作用。内源性性类固醇激素浓度，特别是肥胖相关的雌激素和雄激素在诊断前的升高，在绝经后乳腺癌和子宫内膜癌的发生中起重要作用。脂肪因子脂联素和瘦素以及以急性期C反应蛋白为代表的脂肪细胞介导的慢性低度炎症可能解释了肥胖与结直肠癌风险之间关联的很大一部分。关于这些激素途径是否在其他肥胖相关癌症类型中起中介作用的证据较少。在本章中，我们总结了前瞻性研究中关于循环肥胖相关生物标志物与癌症风险之间关系的分子流行病学证据，同时考虑了孟德尔随机化研究中旨在改善因果推断的现有证据。
