基于欧洲血统的孟德尔随机化证据表明白细胞端粒长度对前列腺癌的因果影响。
Mendelian randomization evidence based on European ancestry for the causal effects of leukocyte telomere length on prostate cancer.
机构信息
Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, China.
出版信息
Hum Genomics. 2024 Jun 3;18(1):56. doi: 10.1186/s40246-024-00622-8.
BACKGROUND
Several lines of evidence suggest that leukocyte telomere length (LTL) can affect the development of prostate cancer (PC).
METHODS
Here, we employed single nucleoside polymorphisms (SNPs) as instrumental variables (IVs) for LTL (n = 472,174) and conducted Mendelian randomization analysis to estimate their causal impact on PCs (79,148 patients/61,106 controls and 6311 patients/88,902 controls).
RESULTS
Every 1-s.d extension of LTL increased the risk of PCs by 34%. Additionally, the analysis of candidate mediators between LTL and PCs via two-step Mendelian randomization revealed that among the 23 candidates, Alzheimer's disease, liver iron content, sex hormone binding global levels, naive CD4-CD8-T cell% T cell, and circulating leptin levels played substantial mediating roles. There is no robust evidence to support the reverse causal relationship between LTL and the selected mediators of PCs. Adjusting for the former four mediators, rather than adjusting for circulating leptin levels, decreased the impact of LTL on PCs.
CONCLUSION
This study provides potential intervention measures for preventing LTL-induced PCs.
背景
有几条证据表明白细胞端粒长度（LTL）可能会影响前列腺癌（PC）的发展。
方法
在这里，我们使用单核苷酸多态性（SNP）作为 LTL 的工具变量（IV）（n=472,174），并进行孟德尔随机化分析，以估计它们对 PC 的因果影响（79,148 名患者/61,106 名对照和 6311 名患者/88,902 名对照）。
结果
LTL 每增加 1 个标准差，PC 的风险就会增加 34%。此外，通过两步孟德尔随机化分析 LTL 与 PC 之间的候选中介物，发现在 23 个候选物中，阿尔茨海默病、肝铁含量、性激素结合球蛋白水平、幼稚 CD4-CD8-T 细胞%T 细胞和循环瘦素水平发挥了重要的中介作用。没有确凿的证据支持 LTL 与 PC 的选定中介物之间的反向因果关系。调整前四个中介物，而不是调整循环瘦素水平，会降低 LTL 对 PC 的影响。
结论
本研究为预防 LTL 诱导的 PC 提供了潜在的干预措施。
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