中心性肥胖和肝癌的关系:两样本孟德尔随机化分析

The relationship between central obesity and hepatocellular carcinoma:a Mendelian randomization study

目的探讨中心性肥胖与肝癌的关系。方法腰围、经BMI矫正的腰围、臀围、经BMI校正的臀围、腰臀比和经BMI校正的腰臀比相关的全基因组关联分析(genome wide association study,GWAS)数据来自欧洲一个包含224459个样本的大型数据库。内脏脂肪体积数据集来自欧洲数据库,包括32860名欧洲受试者的9275407个单核苷酸多态性(single nucleotide polymorphism,SNP)位点信息。肝癌的数据集来自英国生物银行数据库,包括372184名欧洲受试者的汇总数据。对获得的数据集进行两样本孟德尔随机化研究。结果逆方差加权法(IVW)分析结果显示,经BMI矫正的腰围会增加肝癌发生风险(OR=1.001,95%CI:1.000~1.001,P=0.024),且被加权中位数(WM)分析(OR=1.001,95%CI:1.000~1.002,P=0.020)证实,但在MR-Egger回归(OR=1.002,95%CI:0.999~1.004,P=0.135)中未被证实。其他中心性肥胖指标与肝癌无关。结论不同中心性肥胖指标与肝癌的相关性存在差异。经BMI矫正的腰围可能会导致肝癌发生,表明在相对较瘦的人群中,中心性肥胖与肝癌发生相关,且可能存在因果关系。

Objective The relationship between central obesity and hepatocellular carcinoma(HCC)is not completely clear.This study aimed to explore the potential causal associations between central obesity and HCC using Mendelian randomization analysis.Methods Two-sample Mendelian randomization analysis was conducted on the collected data in this study.Genome wide association study(GWAS)data with waist circumference,waist circumference adjusted by body mass index(WCadjBMI),hip circumference,hip circumference adjusted by BMI(HCadjBMI),waist-to-hip ratio and waist-to-hip ratio adjusted by BMI(WHRadjBMI)were obtained from a large-scale database containing 224,459 samples.The visceral fat volume dataset was derived from a European database which included information of 9,275,407 single nucleotide polymorphism(SNP)sites in 32,860 European subjects.The data set for HCC was drawn from the UK Biobank(UKB)database and included aggregated data from 372,184 European subjects.Results Inverse variance weighting(IVW)analysis showed that WCadjBMI increased the risk of HCC(OR=1.001,95%CI(1.000,1.001),P=0.024).This was confirmed by weighted median(WM)analysis(OR=1.001,95%CI(1.000,1.002),P=0.020),but not by MR-Egger regression analysis(OR=1.002,95%CI(0.999,1.004),P=0.135).Other indicators of central obesity were not associated with HCC.Conclusion There exists difference in the abilities of different central obesity indicators to impact on HCC.WCadjBMI may contribute to HCC development,suggesting that in a relatively thin population,central obesity is associated with HCC development with a causal relationship.