端粒长度与前列腺癌的两样本孟德尔随机化研究  

Two-sample Mendelian Randomization Study of Telomere Length and Prostate Cancer

作　　者：杨博文 陈明泉 毕峻铭 姚志豪 曾炜楠 程守钰 张长征 蒋召强 廖航宇 辜晓康 余玉明 YANG Bowen;CHEN Mingquan;BI Junming(Guangdong Cardiovascular Institute,Guangdong Provincial People′s Hospital,Guangdong Academy of Medical Sciences,Guangdong 510080,China)

机构地区：[1]广东省心血管病研究所,广州510080 [2]广东省人民医院、广东省医学科学院,广州510080

出　　处：《医学研究杂志》2025年第3期103-107,共5页Journal of Medical Research

基　　金：广东省财政厅项目(KS0120220268)。

摘　　要：目的采用孟德尔随机化方法分析东亚人群和欧洲人群端粒长度与前列腺癌的因果联系。方法利用已发表的全基因组关联数据,筛选出与端粒长度显著相关的单核苷酸多态性作为工具变量。主要研究方法采用逆方差加权法的随机效应模型进行孟德尔随机化分析。同时,使用孟德尔随机化-Egger法、加权中位数法、简单模式法和加权模式法进行补充分析,以探讨端粒长度与前列腺癌之间的因果关系。此外,通过敏感度分析评估结果的稳健性。结果逆方差加权法分析结果表明,在东亚人群(OR=1.420,95%CI:1.149~1.755,P=0.001)和欧洲人群(OR=1.358,95%CI:1.242~1.484,P=1.727×10^(-11))中,遗传预测的端粒长度与前列腺癌风险之间存在正向因果关联。其余4种分析方法的结果均显示差异有统计学意义(P<0.05),且效应值与逆方差加权法的效应值方向相同。敏感度分析也显示了结果的稳健性。结论在东亚和欧洲人群中,遗传预测的端粒长度较长的个体罹患前列腺癌的风险可能增加。Objective To analyze the causal association of telomere length with prostate cancer in East Asian and European populations using Mendelian randomization.Methods Using published genome-wide association data,single nucleotide polymorphisms significantly associated with telomere length were screened as instrumental variables.The primary research method was Mendelian randomization analysis using a random effects model with inverse variance weighted method.Complementary analyses were also performed using Mendelian randomization-Egger method,weighted median method,simple model and weighted model methods to explore the causal relationship between telomere length and prostate cancer.In addition,the robustness of the results was assessed by sensitivity analyses.Results The results of the inverse variance weighted method analysis showed a positive causal relationship between genetically predicted telomere length and prostate cancer risk in East Asian(OR=1.420,95%CI:1.149-1.755,P=0.001)and European populations(OR=1.358,95%CI:1.242-1.484,P=1.727×10^(-11)).The results of the remaining four analyses showed statistical significance(P<0.05),and the odds ratio was in the same direction as that of the inverse variance weighted method.Sensitivity analyses also showed the robustness of the results.Conclusion Individuals with genetically predicted longer telomere length may be at increased risk of developing prostate cancer in East Asian and European populations.

关 键 词：端粒长度 前列腺癌 孟德尔随机化研究 东亚人群 欧洲人群 

分 类 号：R737.25[医药卫生—肿瘤]