基因预测的爬楼梯频率对肺癌风险的影响:孟德尔随机化研究  

Influence of genetically predicted stair-climbing frequency on the risk of lung cancer:a Mendelian randomization study

作　　者：杨卓林 曹立全[2] 权磊 YANG Zhuolin;CAO Liquan;QUAN Lei(Key Laboratory of Exercise Physiology and Sports Medicine,School of Sports Health,Tianjin University of Sport,Tianjin 301600,China;Laboratory of Physical Education and Health Promotion,Tianjin University of Sport)

机构地区：[1]天津体育学院运动生理学与运动医学重点实验室,天津301600 [2]天津体育学院体卫融合与健康促进实验室

出　　处：《山西医科大学学报》2024年第4期431-438,共8页Journal of Shanxi Medical University

基　　金：科技部国家重点研发项目(2020YFC2006704)。

摘　　要：目的采用孟德尔随机化(Mendelian randomization,MR)探索爬楼梯频率(frequency of stair climbing,FSC)与肺癌(lung cancer,LC)风险之间的因果关系。方法首先,在IEU OpenGWAS数据库中获取FSC、LC风险因素和LC风险的相关全基因组关联研究(genome-wide association study,GWAS)数据;其次,通过MR确定FSC、LC风险因素和LC风险之间的因果联系,并分析体质量指数(body mass index,BMI)、慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)和吸烟行为在FSC与LC风险之间的作用比例;然后,利用连锁不平衡分数回归进一步验证这一关系;最后,通过贝叶斯共定位方法探索可能影响FSC降低LC风险的分子机制。结果MR分析的逆方差加权法(inverse-variance weighting,IVW)结果表明,基于GWAS预测的FSC与LC风险呈现出显著的负因果关系(IVW:OR 0.611,95%CI 0.503~0.743,P=0.011)。在不同类型的肺癌中,FSC与鳞状细胞肺癌(lung squamous cell carcinoma,LUSC)风险(IVW:OR 0.506,95%CI 0.370~0.693,P=0.030)、小细胞肺癌(small cell lung cancer,SCLC)风险(IVW:OR 0.380,95%CI 0.248~0.583,P=0.023)、以及吸烟者肺癌风险(IVW:OR 0.599,95%CI 0.485~0.739,P=0.015)均呈现出显著的负因果关系。此外,BMI(IVW:OR 1.218,95%CI 1.144~1.298,P=0.001)、COPD(IVW:OR 2.003,95%CI 1.652~2.430,P<0.001)和曾经吸烟(IVW:OR 2.139,95%CI 1.731~2.644,P<0.001)与LC风险均呈现出显著的正因果关系,从不吸烟与LC风险呈现出显著的负因果关系(IVW:OR 0.382,95%CI 0.317~0.462,P<0.001)。FSC还与BMI(IVW:OR 0.740,95%CI 0.683~0.802,P<0.001)、COPD(IVW:OR 0.541,95%CI 0.446~0.655,P=0.001)、曾经吸烟(IVW:OR 0.951,95%CI 0.932~0.970,P=0.021)呈现出显著的负因果关系,且与从不吸烟呈现出显著的正因果关系(IVW:OR 1.094,95%CI 1.072~1.116,P<0.001)。多变量MR(multivariable MR,MVMR)结果表明,在FSC与LC风险的因果效应之间,BMI、COPD、曾经吸烟和从不吸烟的介导比例分别为2.2%,78.7%,5.7%和15.2%。连锁不平衡分数回归方法证明了FSCObjective To explore the causal relationship between the frequency of stair climbing(FSC)and the risk of lung cancer(LC)using Mendelian randomization(MR).Methods Firstly,the relevant genome-wide association study(GWAS)data for FSC,LC risk factors,and LC risk were obtained from the IEU OpenGWAS database.Secondly,the causal relationship between FSC,LC risk factors,and LC risk was analyzed by MR,and the proportions of the effects of body mass index(BMI),chronic obstructive pulmonary disease(COPD),and smoking behavior on the relationship between FSC and LC risk were analyzed.Subsequently,this relationship was further validated through linkage disequilibrium score regression.Finally,the molecular mechanisms that may influence the reduction of LC risk by FSC were explored using Bayesian colocalization methods.Results The results of inverse-variance weighting(IVW)in MR analysis indicated a significant negative causal relationship between the predicted FSC based on GWAS and LC risk(IVW:OR 0.611,95%CI 0.503-0.743,P=0.011).In different types of lung cancer,FSC demonstrated significant negative causal relationships with lung squamous cell carcinoma(LUSC)risk(IVW:OR 0.506,95%CI 0.370-0.693,P=0.030),small cell lung cancer(SCLC)risk(IVW:OR 0.380,95%CI 0.248-0.583,P=0.023),and smoker′s lung cancer risk(IVW:OR 0.599,95%CI 0.485-0.739,P=0.015).Furthermore,BMI(IVW:OR 1.218,95%CI 1.144-1.298,P=0.001),COPD(IVW:OR 2.003,95%CI 1.652-2.430,P<0.001),and ever smoking(IVW:OR 2.139,95%CI 1.731-2.644,P<0.001)were significantly positively associated with LC risk,while never smoking showed a significant negative causal relationship with LC risk(IVW:OR 0.382,95%CI 0.317-0.462,P<0.001).FSC also exhibited significant negative causal relationships with BMI(IVW:OR 0.740,95%CI 0.683-0.802,P<0.001),COPD(IVW:OR 1.173,95%CI 1.034-1.331,P=0.001),and ever smoking(IVW:OR 0.951,95%CI 0.932-0.970,P=0.021),and a significant positive causal relationship with never smoking(IVW:OR 1.094,95%CI 1.072-1.116,P<0.001).The mediation proportion of BMI,COPD,ever smo

关 键 词：身体活动 爬楼梯 肺癌 孟德尔随机化 因果效应 

分 类 号：R734.2[医药卫生—肿瘤]