Causal Relationship between Sex Hormone-Binding Globulin and Risk of Neuroblastoma: A Bidirectional Two-Sample Mendelian Randomization Study

作者：Han Wu, Miao Ding, Jiabei Zhu, Siwei Mao, Xiaochen Tang, Sijia Fang, Li Liu, Qiuhui Pan, Chaoyan Yue · 发表于：Cancer Epidemiology Biomarkers & Prevention · 年份：2024 · DOI：10.1158/1055-9965.epi-23-1480 · 被引用次数：2 · 研究领域：Neuroblastoma Research and Treatments、Hypothalamic control of reproductive hormones、Prostate Cancer Treatment and Research

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPAC...