Guan Rijian, Wan Lijun, Zhuang Changshui
1. Department of Urology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
2. Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Urol J. 2024 Nov 27. doi: 10.22037/uj.v21i.8268.
The purpose of this combination research was to examine the relationship between systemic inflammation and the risk of prostate cancer (PCa) through the National Health and Nutrition Examination Survey (NHANES) cross-sectional study and two-sample Mendelian randomization (MR) analysis.
We incorporated NHANES data spanning the years 2001 to 2010, with exposure as systemic inflammation, evaluated using systemic immune-inflammation index (SII) and outcome as PCa, and performed multivariate logistic regression and restricted cubic spline (RCS) to test the correlation between SII and PCa. Further, two-sample MR was used to identify causal associations between specific immune cells and PCa.
A total of 7706 participants (age≥40 years) were included in the analysis in the cross-sectional study, including 350 PCa cases, 7356 controls. Higher SII levels were associated with increased odds of PCa (P<.05). The odds ratio (OR) for PCa was 1.51 (95% CI 1.09-2.08) for the highest versus lowest quartile of SII levels in the fully adjusted model. Also, the RCS analysis showed a threshold effect, with SII levels above 8.90 associated with increased odds of PCa. In addition, MR results suggested a causal relationship between CD62L- monocyte, CD62L- HLA DR+ monocyte, CD14+ CD16+ monocyte, CD62L- Dendritic Cell, Monocytic Myeloid-Derived Suppressor Cell, CD28- CD8dim T cell, CD39+ resting CD4 regulatory T cell and PCa (P<.05).
This combination analysis provides evidence for a significant causal relationship between systemic inflammation and PCa risk. These findings highlight systemic inflammation and inflammatory immune responses as potential modifiable risk factors for PCa.
本联合研究旨在通过美国国家健康与营养检查调查(NHANES)横断面研究及两样本孟德尔随机化(MR)分析,探讨全身炎症与前列腺癌(PCa)风险之间的关系。
我们纳入了2001年至2010年期间的NHANES数据,将全身炎症作为暴露因素,采用全身免疫炎症指数(SII)进行评估,将PCa作为结局,并进行多因素逻辑回归和限制性立方样条(RCS)分析,以检验SII与PCa之间的相关性。此外,采用两样本MR分析来确定特定免疫细胞与PCa之间的因果关联。
横断面研究分析共纳入7706名参与者(年龄≥40岁),包括350例PCa病例和7356例对照。较高的SII水平与PCa发病几率增加相关(P<0.05)。在完全调整模型中,SII水平最高四分位数与最低四分位数相比,PCa的优势比(OR)为1.51(95%CI 1.09 - 2.08)。此外,RCS分析显示存在阈值效应,SII水平高于8.90时,PCa发病几率增加。另外,MR结果表明CD62L - 单核细胞、CD62L - HLA DR + 单核细胞、CD14 + CD16 + 单核细胞、CD62L - 树突状细胞、单核细胞来源的髓系抑制细胞、CD28 - CD8dim T细胞、CD39 + 静息CD4调节性T细胞与PCa之间存在因果关系(P<0.05)。
本联合分析为全身炎症与PCa风险之间存在显著因果关系提供了证据。这些发现突出了全身炎症和炎症免疫反应作为PCa潜在可改变的风险因素。