长期能量平衡相关因素与结直肠癌总生存及代谢沃伯格亚型的关系。
Association between Long-term Energy Balance-Related Factors and Survival in Colorectal Cancer Overall and by Metabolic Warburg-Subtypes.
机构信息
Department of Epidemiology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands.
Department of Pathology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands.
出版信息
Cancer Epidemiol Biomarkers Prev. 2024 Oct 2;33(10):1356-1367. doi: 10.1158/1055-9965.EPI-24-0199.
BACKGROUND
Long-term energy balance-related factors (i.e., lifestyle and physiologic factors that influence the equilibrium between energy intake and energy expenditure over an extended period) such as body mass index (BMI) are linked to colorectal cancer risk, but their impact on colorectal cancer survival is unclear. We explored associations between these long-term energy balance-related factors and survival and examined potential differences across metabolic Warburg-subtypes.
METHODS
Associations between long-term energy balance-related factors and survival in the total series of patients with colorectal cancer (n = 2,347) obtained from the prospective Netherlands Cohort Study, as well as according to Warburg-subtype (Warburg-low: n = 652, Warburg-moderate: n = 802, Warburg-high: n = 797), were investigated using Cox regression analysis.
RESULTS
Among the long-term energy balance-related factors studied, only increasing prediagnostic BMI was associated with a borderline significant poorer overall survival in patients with colorectal cancer [HR5kg/m2, 1.07; 95% confidence interval (CI), 0.99-1.15]. Stratified analyses showed that prediagnostic weight gain (HR5kg, 1.04; 95% CI, 0.99-1.09) and potentially increased height (HR5cm, 1.04; 95% CI, 0.98-1.11) were associated with poor overall survival only in patients with Warburg-high colorectal cancer. Increasing prediagnostic BMI was associated with poor survival only in patients with Warburg-moderate colorectal cancer (colorectal cancer-specific: HR5kg/m2, 1.12; 95% CI, 0.96-1.32; overall: HR5kg/m2, 1.20; 95% CI, 1.05-1.36). No consistent patterns were observed across energy restriction proxies.
CONCLUSIONS
Maintaining a healthy prediagnostic BMI may be beneficial for colorectal cancer survival. Moreover, associations between prediagnostic BMI, weight change, early-life energy restriction, height, and colorectal cancer survival differed according to Warburg-subtypes.
IMPACT
Understanding the biologic pathways involved in associations between energy balance-related factors and colorectal cancer survival could help refine prevention strategies in the future.
背景
长期的能量平衡相关因素（即在较长时间内影响能量摄入和能量消耗平衡的生活方式和生理因素，例如体重指数（BMI））与结直肠癌风险相关，但它们对结直肠癌生存的影响尚不清楚。我们探讨了这些长期能量平衡相关因素与生存之间的关联，并检查了它们在代谢型 Warburg 亚型之间的潜在差异。
方法
从前瞻性荷兰队列研究中获得的 2347 例结直肠癌患者的总系列中，以及根据 Warburg 亚型（Warburg-低：n=652，Warburg-中：n=802，Warburg-高：n=797），使用 Cox 回归分析研究了长期能量平衡相关因素与生存之间的关联。
结果
在所研究的长期能量平衡相关因素中，仅诊断前 BMI 的增加与结直肠癌患者的总生存有边缘显著的不良相关[每增加 5kg/m2 的 HR，1.07；95%置信区间（CI），0.99-1.15]。分层分析表明，诊断前体重增加（每增加 5kg 的 HR，1.04；95%CI，0.99-1.09）和潜在的身高增加（每增加 5cm 的 HR，1.04；95%CI，0.98-1.11）仅与 Warburg-高结直肠癌患者的总体生存不良相关。诊断前 BMI 的增加仅与 Warburg-中结直肠癌患者的生存不良相关（结直肠癌特异性：每增加 5kg/m2 的 HR，1.12；95%CI，0.96-1.32；总体：每增加 5kg/m2 的 HR，1.20；95%CI，1.05-1.36）。没有观察到能量限制替代指标之间的一致模式。
结论
保持健康的诊断前 BMI 可能有益于结直肠癌的生存。此外，诊断前 BMI、体重变化、生命早期能量限制、身高与结直肠癌生存之间的关联因 Warburg 亚型而异。
影响
了解能量平衡相关因素与结直肠癌生存之间关联的生物学途径，有助于未来制定更精细的预防策略。
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