Table3_A causal link between circulating leukocytes and three major urologic cancers: a mendelian randomization investigation.docx

PurposeThis study aimed to explore the influence of serum leukocytes on urologic cancers (UC) using observation-based investigations. In the present study, Mendelian randomization (MR) was employed to assess the link between leukocyte count (LC) and the risk of UC development.
MethodsFive LC and three major UC patient prognoses were obtained for MR analysis from genome-wide association studies (GWAS). Furthermore, in order to evaluate reverse causality, bidirectional studies were conducted. Finally, a sensitivity analysis using multiple methods was carried out.
ResultsThere was no significant correlation found in the genetic assessment of differential LC between the co-occurrence of bladder cancer (BCA) and renal cell carcinoma (RCC). Conversely, an individual 1-standard deviation (SD) rise in neutrophil count was strongly linked to a 9.3% elevation in prostate cancer (PCA) risk ([odd ratio]OR = 1.093, 95% [confidence interval]CI = 0.864–1.383, p = 0.002). Reverse MR analysis suggested that PCA was unlikely to cause changes in neutrophil count. Additional sensitivity studies revealed that the outcomes of all MR evaluations were similar, and there was no horizontal pleiotropy. Primary MR analysis using inverse-variance weighted (IVW) revealed that differential lymphocyte count significantly influenced RCC risk (OR = 1.162, 95%CI = 0.918–1.470, p = 0.001). Moreover, altered basophil count also affected BCA risk (OR = 1.249, 95% CI = 0.904–1.725, p = 0.018). Nonetheless, these causal associations were not significant in the sensitivity analysis.
ConclusionIn summary, the results revealed that increased neutrophil counts represent a significant PCA risk factor. The current research indicates a significant relationship between immune cell activity and the cause of UC.

本研究旨在通过观察性研究探讨血清白细胞对泌尿生殖系统癌症（urologic cancers, UC）的影响。本研究采用孟德尔随机化（Mendelian randomization, MR）方法，评估白细胞计数（leukocyte count, LC）与泌尿生殖系统癌症发病风险之间的关联。

本研究从全基因组关联研究（genome-wide association studies, GWAS）中获取了5项白细胞分类计数相关数据及3项主要泌尿生殖系统癌症患者的预后数据，用于孟德尔随机化分析。此外，为评估反向因果关联，本研究开展了双向孟德尔随机化研究。最终，采用多种方法完成了敏感性分析。

遗传关联分析显示，白细胞分类计数与膀胱癌（bladder cancer, BCA）和肾细胞癌（renal cell carcinoma, RCC）的共发风险无显著相关性。与之相反，中性粒细胞计数每升高1个标准差（standard deviation, SD），前列腺癌（prostate cancer, PCA）的发病风险即显著升高9.3%（比值比[odd ratio, OR]=1.093，95%置信区间[confidence interval, CI]=0.864~1.383，p=0.002）。反向孟德尔随机化分析提示，前列腺癌不太可能导致中性粒细胞计数发生改变。额外敏感性研究表明，所有孟德尔随机化评估结果均一致，且未发现水平多效性。采用逆方差加权（inverse-variance weighted, IVW）法开展的核心孟德尔随机化分析显示，淋巴细胞亚群计数异常可显著影响肾细胞癌发病风险（OR=1.162，95%CI=0.918~1.470，p=0.001）。此外，嗜碱性粒细胞计数异常也会影响膀胱癌发病风险（OR=1.249，95%CI=0.904~1.725，p=0.018）。不过，上述因果关联在敏感性分析中未显示出统计学显著性。

综上，本研究结果表明，中性粒细胞计数升高是前列腺癌发病的显著危险因素。本研究证实，免疫细胞活性与泌尿生殖系统癌症的发病机制存在显著关联。