Zhi-Gang Yi, Han-Dong Wang
Department of Nephrology, Huangshi Aikang Hospital Affiliated to Hubei Polytechnic University, Huangshi, Hubei, China.
Front Genet. 2024 Jun 19;15:1424119. doi: 10.3389/fgene.2024.1424119. eCollection 2024.
This 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.
Five 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.
There 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, = 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, = 0.001). Moreover, altered basophil count also affected BCA risk (OR = 1.249, 95% CI = 0.904-1.725, = 0.018). Nonetheless, these causal associations were not significant in the sensitivity analysis.
In 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.
本研究旨在通过基于观察的调查探讨血清白细胞对泌尿系统癌症(UC)的影响。在本研究中,采用孟德尔随机化(MR)方法评估白细胞计数(LC)与UC发生风险之间的联系。
从全基因组关联研究(GWAS)中获取5个LC和3个主要UC患者预后指标用于MR分析。此外,为评估反向因果关系,进行了双向研究。最后,使用多种方法进行了敏感性分析。
在膀胱癌(BCA)和肾细胞癌(RCC)共存时,差异LC的基因评估中未发现显著相关性。相反,中性粒细胞计数每增加1个标准差(SD),前列腺癌(PCA)风险强烈关联升高9.3%(比值比[OR]=1.093,95%置信区间[CI]=0.864-1.383,P=0.002)。反向MR分析表明,PCA不太可能导致中性粒细胞计数变化。额外的敏感性研究表明,所有MR评估结果相似,且不存在水平多效性。使用逆方差加权(IVW)的主要MR分析表明,差异淋巴细胞计数显著影响RCC风险(OR=1.162,95%CI=0.918-1.470,P=0.001)。此外,嗜碱性粒细胞计数改变也影响BCA风险(OR=1.249,95%CI=0.904-1.725,P=0.018)。然而,这些因果关联在敏感性分析中并不显著。
总之,结果显示中性粒细胞计数增加是PCA的一个重要危险因素。当前研究表明免疫细胞活性与UC病因之间存在显著关系。