251 Airforce General Hospital, Kanellopoulou 3, 11525, Athens, Greece.
Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA.
Metabolism. 2019 Mar;92:121-135. doi: 10.1016/j.metabol.2018.11.001. Epub 2018 Nov 13.
Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype.
肥胖相关恶性肿瘤的发病率不断上升，使这一疾病谱成为公共卫生的重点。在全球范围内，肥胖导致的癌症负担（以人群归因分数表示）在男性中为 11.9%，在女性中为 13.1%。有确凿的证据表明，超重与至少 13 个解剖部位的癌症风险增加有关，包括子宫内膜、食管、肾和胰腺腺癌；肝细胞癌；贲门癌；脑膜瘤；多发性骨髓瘤；结直肠癌、绝经后乳腺癌、卵巢癌、胆囊癌和甲状腺癌。我们首先综合了当前的流行病学证据；癌症风险和死亡率中的肥胖悖论；体重增加和体重减轻在调节癌症风险中的作用；肥胖和癌症研究中可靠的人体测量指标；以及与肥胖相关的癌症中的性别差异。我们批判性地总结了将肥胖与癌症联系起来的新兴生物学机制，包括胰岛素抵抗和 IGF-I 系统和信号的异常；性激素生物合成和途径；亚临床慢性低度炎症和氧化应激；脂肪细胞因子病理生理学的改变；来自异位脂肪沉积的因素；微环境和细胞扰动，包括血管扰动、上皮-间充质转化、内质网应激和迁移脂肪祖细胞；昼夜节律的破坏；膳食营养素；具有潜在意义的因素，如改变的肠道微生物组；以及肥胖和癌症中的力学因素。讨论了未来在预防、诊断和治疗方面的前景。本综述的目的是研究这些主要潜在机制和危险因素的相互作用如何对靶组织发挥作用，使其获得癌变表型。
