Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cancer Epidemiol Biomarkers Prev. 2024 Jun 3;33(6):846-853. doi: 10.1158/1055-9965.EPI-23-1480.
The causal relationship between sex hormone-binding globulin (SHBG) and neuroblastoma remains unknown. This study aimed to explore the causality between SHBG and the risk of neuroblastoma using bidirectional two-sample Mendelian randomization (MR) study.
Instrumental variables associated with SHBG were obtained from the genome-wide association study (GWAS) of European containing 214,989 females and 185,221 males from the UK Biobank. Summary-level data for neuroblastoma were derived from the IEU OpenGWAS project with 1,627 patients and 3,254 controls. The inverse-variance weighted (IVW) method served as the primary analytic tool.
The IVW method revealed a significant positive causal relationship between male SHBG and the risk of neuroblastoma [OR, 2.169; 95% confidence interval (CI), 1.207-3.897; P = 0.010]. Conversely, female SHBG showed no significant causal link with neuroblastoma (IVW OR, 1.004; 95% CI, 0.542-1.860; P = 0.990). No significant reverse causality was detected. Sensitivity analyses validated these findings.
Elevated SHBG levels in males, but not in females, can causally increase the risk of neuroblastoma. This gender-specific effect indicates a potential differential role of SHBG in the etiology of neuroblastoma. Further research is needed to elucidate the underlying mechanisms of this gender disparity. Monitoring SHBG levels, especially in males, could be pivotal in neuroblastoma risk assessment and management.
This study highlights a novel gender-specific aspect in the risk of neuroblastoma, emphasizing the potential role of male SHBG levels in neuroblastoma incidence, and sets the stage for targeted preventative strategies and further investigation into gender-based biological mechanisms.
性激素结合球蛋白 (SHBG) 与神经母细胞瘤之间的因果关系尚不清楚。本研究旨在使用双向两样本 Mendelian 随机化 (MR) 研究来探讨 SHBG 与神经母细胞瘤风险之间的因果关系。
从英国生物库中包含的 214989 名女性和 185221 名男性的全基因组关联研究 (GWAS) 中获得与 SHBG 相关的工具变量。神经母细胞瘤的汇总水平数据来自 IEU OpenGWAS 项目，包含 1627 名患者和 3254 名对照。逆方差加权 (IVW) 方法作为主要分析工具。
IVW 方法表明，男性 SHBG 与神经母细胞瘤风险之间存在显著正因果关系 [比值比 (OR)，2.169；95%置信区间 (CI)，1.207-3.897；P=0.010]。相反，女性 SHBG 与神经母细胞瘤无显著因果关系 (IVW OR，1.004；95%CI，0.542-1.860；P=0.990)。未检测到显著的反向因果关系。敏感性分析验证了这些发现。
男性 SHBG 水平升高（但女性 SHBG 水平没有升高）可导致神经母细胞瘤风险增加。这种性别特异性效应表明 SHBG 在神经母细胞瘤发病机制中可能具有潜在的不同作用。需要进一步研究阐明这种性别差异的潜在机制。监测 SHBG 水平，特别是男性的 SHBG 水平，可能对神经母细胞瘤风险评估和管理具有重要意义。
本研究强调了神经母细胞瘤风险中的一个新的性别特异性方面，突出了男性 SHBG 水平在神经母细胞瘤发病中的潜在作用，并为针对男性的预防策略和进一步研究性别相关的生物学机制奠定了基础。
