Xu Manrong, Li Menghan, Zhang Yawen, Li Lianxi, Shen Yun, Hu Gang
Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Diabetes Obes Metab. 2025 Sep;27(9):5291-5301. doi: 10.1111/dom.16582. Epub 2025 Jul 2.
The definition of clinical obesity was newly announced. Our study aims to investigate the relationship between different states of obesity and dysfunctions due to obesity with cancer incidence and mortality.
The prospective cohort study from the UK Biobank included 220 016 participants. Anthropometric parameters, in combination with obesity-induced dysfunctions, were used to diagnose clinical obesity. Six clusters were categorized according to individual's baseline and follow-up dysfunction status. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for cancer incidence risk were estimated using the landmark analysis.
After a mean follow-up period of 11.0 years, a total of 24 066 cancer incidence was observed. Using Cluster 1 (participants without obesity and dysfunction at baseline and during follow-up) as the reference group, Cluster 5 (preclinical obesity with follow-up dysfunctions; HR = 3.17, 95% CI: 3.05-3.29) exhibited the highest multivariable-adjusted cancer incidence risk, while Cluster 4 (preclinical obesity without follow-up dysfunctions; HR = 0.88, 95% CI: 0.85-0.92) showed the lowest. Additionally, the fully adjusted HRs for cancer mortality showed the highest in Cluster 6 (clinical obesity; HR = 1.82, 95% CI: 1.65-2.00), compared with Cluster 1. Site-specific analyses showed consistently higher cancer risks in Cluster 5 and 6 across various types of cancer, notably the incidence of pancreatic cancer and the mortality of prostate or bladder cancer.
Obesity-induced dysfunction was significantly associated with cancer risk. For future clinical practice, the early identification and intervention of clinical obesity and obesity-induced dysfunctions are of critical importance for reducing cancer risks.
临床肥胖的定义刚刚公布。我们的研究旨在调查不同肥胖状态及肥胖所致功能障碍与癌症发病率和死亡率之间的关系。
来自英国生物银行的前瞻性队列研究纳入了220016名参与者。人体测量参数结合肥胖引起的功能障碍用于诊断临床肥胖。根据个体的基线和随访功能状态分为六个组。使用地标性分析估计癌症发病风险的风险比（HRs）及相应的95%置信区间（CIs）。
平均随访11.0年后，共观察到24066例癌症发病。以第1组（基线和随访期间无肥胖和功能障碍的参与者）作为参照组，第5组（临床前肥胖伴随访功能障碍；HR = 3.17，95% CI：3.05 - 3.29）显示出最高的多变量调整癌症发病风险，而第4组（临床前肥胖无随访功能障碍；HR = 0.88，95% CI：0.85 - 0.92）风险最低。此外，与第1组相比，癌症死亡率的完全调整HRs在第6组（临床肥胖；HR = 1.82，95% CI：1.65 - 2.00）中最高。特定部位分析显示，在第5组和第6组中，各类癌症的风险一直较高，尤其是胰腺癌的发病率以及前列腺癌或膀胱癌的死亡率。
肥胖引起的功能障碍与癌症风险显著相关。对于未来的临床实践，早期识别和干预临床肥胖及肥胖引起的功能障碍对于降低癌症风险至关重要。
