肾细胞癌 (RCC) 患者的体重指数 (BMI) 与死亡率之间的关系存在争议，一些观察性研究表明，BMI 越高，死亡率越低。然而，混杂因素和反向因果关系等方法论问题可能会使这些发现产生偏差。使用 BMI 相关的遗传变异可以避免这些偏差并生成更有效的估计。在这项前瞻性队列研究中，我们纳入了来自英国生物银行的 1264 名 RCC 患者（446 例死亡）。我们根据 336 个 BMI 相关基因变异创建了 BMI 多基因评分 (PGS)。通过逻辑回归（所有 RCC 病例）和 Cox 回归（906 例病例）评估 PGS 与死亡率（全因死亡率和 RCC 特异性死亡率）之间的关联。为了进行比较，通过事件病例中的 Cox 回归对测量的诊断前 BMI 和腰臀比 (WHR) 与死亡率的关联进行了量化。我们根据人体测量和 RCC 诊断之间的时间对这些分析进行分层，以评估反向因果关系的影响。我们没有观察到 RCC 患者中 BMI PGS 与全因死亡率之间的关联（每 SD 增加的风险比 (HR) = 0.98， 95% CI: 0.88,1.10)。未发现诊断前BMI（每增加5kg/m2的HR= 0.93，95％CI：0.83，1.04）或WHR（每0.1增加的HR= 0.97，95％CI：0.83，1.13）与死亡率之间存在关联。在RCC诊断前2年内进行人体测量的患者中，我们观察到较高BMI（HR每5kg/m2= 0.76，95％CI：0.59，0.98）和WHR（HR =每0.1增加0.67，95％CI：0.59，0.98）之间的关联： 0.45,0.98)，死亡风险较低。 RCC 特异性死亡率也观察到类似的模式。我们发现，高 BMI 的遗传变异或测量的诊断前身体肥胖与 RCC 患者的死亡率之间没有关联，我们的结果表明，肥胖与较低体重之间存在反向因果关系。死亡。未来的研究应仔细设计，以产生能够解释混杂因素和反向因果关系的公正估计。© 2024。作者，获得施普林格自然有限公司的独家许可。

The association between body mass index (BMI) and mortality among individuals with renal cell cancer (RCC) is debated, with some observational studies suggesting a lower mortality associated with higher BMI. However, methodological issues such as confounding and reverse causation may bias these findings. Using BMI-associated genetic variants can avoid these biases and generate more valid estimates.In this prospective cohort study, we included 1264 RCC patients (446 deaths) from the UK Biobank. We created a BMI polygenic score (PGS) based on 336 BMI-associated genetic variants. The association between the PGS and mortality (all-cause and RCC-specific) was evaluated by logistic regression (all RCC cases) and Cox regression (906 incident cases). For comparison, the associations of measured pre-diagnostic BMI and waist-to-hip ratio (WHR) with mortality were quantified by Cox regression among incident cases. We stratified these analyses by time between anthropometric measurement and RCC diagnosis to assess the influence of reverse causation.We did not observe an association between the BMI PGS and all-cause mortality among RCC patients (hazard ratio (HR) per SD increase = 0.98, 95% CI: 0.88,1.10). No association was found for pre-diagnostic BMI (HR per 5 kg/m2 increase = 0.93, 95% CI: 0.83,1.04) or WHR (HR per 0.1 increase = 0.97, 95% CI: 0.83,1.13) with mortality. In patients with anthropometrics measured within 2 years before RCC diagnosis, we observed associations of higher BMI (HR per 5 kg/m2 = 0.76, 95% CI: 0.59,0.98) and WHR (HR = 0.67 per 0.1 increase, 95% CI: 0.45,0.98) with a lower risk of death. Similar patterns were observed for RCC-specific mortality.We found no association between either genetic variants for high BMI or measured pre-diagnostic body adiposity and mortality among RCC patients, and our results suggested a role for reverse causation in the association of obesity with lower mortality. Future studies should be designed carefully to produce unbiased estimates that account for confounding and reverse causation.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.