Trevellin Elisabetta, Bettini Silvia, Pilatone Anna, Vettor Roberto, Milan Gabriella
Center for the Study and Integrated Treatment of Obesity (CeSTIO), Internal Medicine 3, Department of Medicine, University Hospital of Padova, 35128 Padova, Italy.
Biomedicines. 2023 Apr 28;11(5):1319. doi: 10.3390/biomedicines11051319.
Epidemiological observations, experimental studies and clinical data show that obesity is associated with a higher risk of developing different types of cancer; however, proof of a cause-effect relationship that meets the causality criteria is still lacking. Several data suggest that the adipose organ could be the protagonist in this crosstalk. In particular, the adipose tissue (AT) alterations occurring in obesity parallel some tumour behaviours, such as their theoretically unlimited expandability, infiltration capacity, angiogenesis regulation, local and systemic inflammation and changes to the immunometabolism and secretome. Moreover, AT and cancer share similar morpho-functional units which regulate tissue expansion: the adiponiche and tumour-niche, respectively. Through direct and indirect interactions involving different cellular types and molecular mechanisms, the obesity-altered adiponiche contributes to cancer development, progression, metastasis and chemoresistance. Moreover, modifications to the gut microbiome and circadian rhythm disruption also play important roles. Clinical studies clearly demonstrate that weight loss is associated with a decreased risk of developing obesity-related cancers, matching the reverse-causality criteria and providing a causality correlation between the two variables. Here, we provide an overview of the methodological, epidemiological and pathophysiological aspects, with a special focus on clinical implications for cancer risk and prognosis and potential therapeutic interventions.
流行病学观察、实验研究和临床数据表明，肥胖与患不同类型癌症的风险较高相关；然而，仍缺乏符合因果关系标准的因果关系证据。一些数据表明，脂肪器官可能是这种相互作用的主角。特别是，肥胖时发生的脂肪组织（AT）改变与一些肿瘤行为相似，如理论上无限的扩张能力、浸润能力、血管生成调节、局部和全身炎症以及免疫代谢和分泌组的变化。此外，AT和癌症具有相似的调节组织扩张的形态功能单位，分别是脂肪龛和肿瘤龛。通过涉及不同细胞类型和分子机制的直接和间接相互作用，肥胖改变的脂肪龛促进癌症的发生、发展、转移和化疗耐药性。此外，肠道微生物群的改变和昼夜节律紊乱也起着重要作用。临床研究清楚地表明，体重减轻与患肥胖相关癌症的风险降低相关，符合反向因果关系标准，并提供了这两个变量之间的因果关系。在此，我们概述了方法学、流行病学和病理生理学方面，特别关注癌症风险和预后的临床意义以及潜在的治疗干预措施。
