Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA.
Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Semin Cancer Biol. 2023 Sep;94:21-33. doi: 10.1016/j.semcancer.2023.06.001. Epub 2023 Jun 5.
Obesity, defined by body mass index (BMI), is an established risk factor for specific renal cell carcinoma (RCC) subtypes such as clear cell RCC, the most common RCC histology. Many studies have identified an association between obesity and improved survival after diagnosis of RCC, a potential "obesity paradox." Clinically, there is uncertainty whether improved outcomes observed after diagnosis are driven by stage, type of treatment received, or artifacts of longitudinal changes in weight and body composition. The biological mechanisms underlying obesity's influence on RCC are not fully established, but multiomic and mechanistic studies suggest an impact on tumor metabolism, particularly fatty acid metabolism, angiogenesis, and peritumoral inflammation, which are known to be key biological hallmarks of clear cell RCC. Conversely, high-intensity exercise associated with increased muscle mass may be a risk factor for renal medullary carcinoma, a rare RCC subtype that predominantly occurs in individuals with sickle hemoglobinopathies. Herein, we highlight methodologic challenges associated with studying the influence of obesity on RCC and review the clinical evidence and potential underlying mechanisms associating RCC with BMI and body composition.
肥胖症是由体重指数 (BMI) 定义的，它是特定肾细胞癌 (RCC) 亚型的既定危险因素，如透明细胞 RCC，这是最常见的 RCC 组织学类型。许多研究已经确定肥胖症与 RCC 诊断后生存改善之间存在关联，这是一种潜在的“肥胖悖论”。临床上，尚不确定诊断后观察到的改善结果是由分期、所接受的治疗类型还是体重和身体成分的纵向变化的假象驱动的。肥胖症对 RCC 影响的生物学机制尚未完全确定，但多组学和机制研究表明，肥胖症会影响肿瘤代谢，特别是脂肪酸代谢、血管生成和肿瘤周围炎症，这些都是透明细胞 RCC 的已知关键生物学特征。相反，与肌肉量增加相关的高强度运动可能是肾髓质癌的一个危险因素，肾髓质癌是一种罕见的 RCC 亚型，主要发生在镰状细胞血红蛋白病患者中。本文强调了研究肥胖症对 RCC 的影响所涉及的方法学挑战，并回顾了与 BMI 和身体成分相关的与 RCC 相关的临床证据和潜在机制。
