摘要
目的 采用孟德尔随机化(MR)方法探究肥胖、外周血血脂指标与非小细胞肺癌(NSCLC)的因果关系,为制定NSCLC防控策略提供依据.方法 通过全基因组关联研究(GWAS)及相关公开数据库收集体质指数(BMI)、体脂率(BFR)、腰臀比(WHR)3种肥胖评价指标,以及三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)和脂蛋白a[LP(a)]7种外周血血脂指标资料,采用随机效应模型的逆方差加权法和多因素MR分析肥胖、外周血血脂指标与NSCLC的因果关系.采用Co-chran Q检验和MR-Egger回归法评估工具变量的异质性和水平多效性.结果 BMI与NSCLC存在统计学关联(OR=1.256,95%CI:1.087～1.451);BFR、WHR及7种外周血血脂指标与NSCLC无统计学关联(均P＞0.005).BMI、BFR、WHR、TG、HDL-C与NSCLC的关联存在异质性(均P＜0.05);未发现工具变量的水平多效性(均P＞0.05).调整BFR后,BMI与NSCLC无统计学关联(OR=1.367,95%CI:0.878～2.128);分别调整WHR、外周血血脂指标后,BMI与NSCLC仍有统计学关联(均P＜0.05).结论 BMI升高与NSCLC发病风险升高有关,BFR是BMI与NSCLC关联的潜在影响因素.
Abstract
Objective To examine the causal relationships between obesity,peripheral blood lipid indicators and non-small cell lung cancer(NSCLC)using Mendelian randomization(MR)method,so as to provide the basis for developing NSCLC prevention and control strategies.Methods Genetic variation data of three obesity evaluation indicators,includ-ing body mass index(BMI),body fat ratio(BFR)and waist-to-hip ratio(WHR),and seven peripheral blood lipid indica-tors,including triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipopro-tein cholesterol(HDL-C),apolipoprotein A1(ApoA1),apolipoprotein B(ApoB)and lipoprotein a[LP(a)]were collected through genome-wide association studies(GWAS)and related public databases.Potential causal relationships between obesity,peripheral blood lipid indicators and NSCLC were analyzed using inverse-variance weighted(IVW)method and multivariable MR analysis upon a random effect model.Heterogeneity and horizontal pleiotropy of instrumental variables were evaluated using Cochran's Q test and MR-Egger regression.Results There was statistically association between BMI with NSCLC(OR=1.256,95%CI:1.087-1.451);there were no statistically associations between BFR,WHR,seven peripheral blood lipid indicators and NSCLC(all P>0.005).There was heterogeneity in the association between BMI,BFR,WHR,TG,HDL-C and NSCLC(all P<0.05);no horizontal pleiotropy of instrumental variables was found(all P>0.05).There was no statistically association between BMI and NSCLC after adjusting BFR(OR=1.367,95%CI:0.878-2.128);there was still statistically association between BMI and NSCLC after adjusting WHR and peripheral blood lipid indicators(both P<0.05).Conclusions The increase of BMI is associated with the increased risk of NSCLC incidence.BFR may be a potential influencing factor for the association between BMI and NSCLC.
维普
万方数据