Christakoudi Sofia, Tsilidis Konstantinos K, Gunter Marc J, Riboli Elio
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, White City Campus, 90 Wood Lane, London, W12 0BZ, UK.
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
J Inflamm (Lond). 2025 Aug 11;22(1):31. doi: 10.1186/s12950-025-00458-6.
Kidney cancer is related to obesity and inflammation and platelets are involved in thrombo-inflammation, but the prospective associations of individual leucocyte subtypes and platelet parameters with kidney cancer risk are unclear.
Using data from the UK Biobank cohort and multivariable Cox proportional hazards models, we obtained hazard ratios (HR per one standard deviation increase) with 95% confidence intervals (95%CI) for the mutually adjusted associations of inflammatory markers and platelet parameters (log-transformed), and allometric obesity indices (body mass index (BMI), a body shape index (ABSI), hip index) with kidney cancer risk (overall, by sex, and by follow-up time with a cut-off at 6 years).
During a mean follow-up of 10.4 years, 1086 kidney cancers were ascertained in 396,482 participants. Conditional on each other and covariates, neutrophil count (HR = 1.12; 95%CI = 1.04 - 1.20), C-reactive protein (HR = 1.11; 95%CI = 1.04 - 1.19), platelet count (HR = 1.18; 95%CI = 1.10 - 1.27), platelet distribution width (HR = 1.16; 95%CI = 1.09 - 1.24), and BMI (HR = 1.22; 95%CI = 1.14 - 1.30) were positively associated, while lymphocyte count (HR = 0.90; 95%CI = 0.84 - 0.96) and hip index (HR = 0.88; 95%CI = 0.83 - 0.93) were inversely associated with kidney cancer risk in participants overall, but there was little evidence for an association with ABSI (HR = 1.05; 95%CI = 0.99 - 1.12). There were no major sex differences, but the positive association with C-reactive protein was observed only for shorter follow-up time (HR = 1.26; 95%CI = 1.14 - 1.38; p-follow-up = 0.0006).
Our findings support two separate longer-acting pathways in kidney cancer development- a pathway related to general rather than abdominal obesity and an immune-cell-related pathway involving neutrophils assisted by activated platelets, as well as a cancer-induced thrombo-inflammation closer to kidney cancer diagnosis.
肾癌与肥胖和炎症相关，且血小板参与血栓炎症过程，但个体白细胞亚型和血小板参数与肾癌风险的前瞻性关联尚不清楚。
利用英国生物银行队列的数据和多变量Cox比例风险模型，我们获得了炎症标志物和血小板参数（对数转换）以及异速生长肥胖指数（体重指数（BMI）、体型指数（ABSI）、髋部指数）与肾癌风险（总体、按性别以及按随访时间（以6年为界））相互调整后的关联的风险比（每增加一个标准差的HR）及95%置信区间（95%CI）。
在平均10.4年的随访期间，396482名参与者中确诊了1086例肾癌。在相互调整及协变量调整后，总体参与者中，中性粒细胞计数（HR = 1.12；95%CI = 1.04 - 1.20）、C反应蛋白（HR = 1.11；95%CI = 1.04 - 1.19）、血小板计数（HR = 1.18；95%CI = 1.10 - 1.27）、血小板分布宽度（HR = 1.16；95%CI = 1.09 - 1.24）和BMI（HR = 1.22；95%CI = 1.14 - 1.30）与肾癌风险呈正相关，而淋巴细胞计数（HR = 0.90；95%CI = 0.84 - 0.96）和髋部指数（HR = 0.88；95%CI = 0.83 - 0.93）与肾癌风险呈负相关，但几乎没有证据表明与ABSI有关联（HR = 1.05；95%CI = 0.99 - 1.12）。没有明显的性别差异，但仅在较短随访时间内观察到与C反应蛋白的正相关（HR = 1.26；95%CI = 1.14 - 1.38；随访时间p值 = 0.0006）。
我们的研究结果支持肾癌发展过程中两条独立的长效途径——一条与全身肥胖而非腹部肥胖相关的途径，以及一条与免疫细胞相关的途径，该途径涉及由活化血小板辅助的中性粒细胞，还有一条在接近肾癌诊断时由癌症引发的血栓炎症途径。
