Hillon P, Guiu B, Vincent J, Petit J-M
Université de Bourgogne, CHU de Dijon, rue de l'église, Dijon, France.
Gastroenterol Clin Biol. 2010 Oct;34(10):529-33. doi: 10.1016/j.gcb.2010.07.021.
The frequency of obesity has been increasing worldwide for 20 years. Many epidemiological studies support a correlation between obesity and increased risk of cancer, particularly digestive cancers in both genders, and gynaecological cancer in women. Currently, about 5% of cancers could be directly related to overweight. Carcinogenesis mechanisms induced by obesity involve insulin resistance, adipokine and angiogenic factor secretions, and inflammation. Experimental and clinical evidence suggest that insulin resistance plays a major role in carcinogenesis. Insulin and non-protein banded IGF-1, whose levels are increased in type 2 diabetes, stimulate cellular growth and inhibit apoptosis. Abnormalities in adipokine secretion by the central adipose tissue play a role at different stages of obesity-induced carcinogenesis. Excess of leptin and PAI-1, associated with a decrease in adiponectin secretion in obese people, contributes to carcinogenesis through cellular growth and angiogenesis stimulation. Remodelling of the extracellular matrix due to metalloproteinase stimulation by PAI-1 is also able to promote cell migration. Obesity not only increases cancer frequency, but is also liable to modify the prognosis and the response to antiangiogenic therapy of digestive cancers. This data suggests the need for clinicians to take into account overweight in cancer risk evaluation and to consider obesity and metabolic disorders as confounding factors in designing therapeutic studies.
20年来，肥胖症的发病率在全球范围内一直在上升。许多流行病学研究支持肥胖与癌症风险增加之间存在关联，尤其是男女的消化系统癌症以及女性的妇科癌症。目前，约5%的癌症可能与超重直接相关。肥胖诱导的致癌机制涉及胰岛素抵抗、脂肪因子和血管生成因子的分泌以及炎症。实验和临床证据表明，胰岛素抵抗在致癌过程中起主要作用。胰岛素和非蛋白结合型IGF-1在2型糖尿病患者中水平升高，它们刺激细胞生长并抑制细胞凋亡。中央脂肪组织脂肪因子分泌异常在肥胖诱导的致癌过程的不同阶段发挥作用。肥胖人群中瘦素和PAI-1过多，同时脂联素分泌减少，通过刺激细胞生长和血管生成促进致癌作用。PAI-1刺激金属蛋白酶导致细胞外基质重塑，也能够促进细胞迁移。肥胖不仅会增加癌症发病率，还可能改变消化系统癌症的预后以及对抗血管生成治疗的反应。这些数据表明，临床医生在癌症风险评估中需要考虑超重因素，并在设计治疗研究时将肥胖和代谢紊乱视为混杂因素。
