临床与病理杂志2024，Vol.44Issue(11)：1488-1495,8.DOI:10.11817/j.issn.2095-6959.2024.240602
基于孟德尔随机化的二手烟与结直肠癌因果关系及代谢物的中介作用
Causal relationship between second-hand smoke and colorectal cancer and the mediating role of metabolites:A Mendelian randomization study
摘要
Abstract
Objective:Colorectal cancer(CRC)ranks third globally in cancer incidence(9.6%).While active smoking is known to increase CRC risk,the effect and underlying mechanism of second-hand smoke exposure remain unclear.This study aims to investigate the causal relationship between second-hand smoke exposure and CRC using Mendelian randomization(MR)and to evaluate the potential mediating role of blood metabolites. Methods:A two-sample MR analysis was performed using data from genome-wide association analysis(GWAS)to assess the relationship between second-hand smoke exposure(at home and outside the home)and CRC.Genetic variants strongly associated with second-hand smoke were selected as instrumental variables.MR analyses were conducted using inverse variance weighted(IVW),MR-Egger regression,weighted median,and weighted mode methods to determine causality,and sensitivity analyses were performed to ensure robustness.Furthermore,MR was used to evaluate the mediating role of blood metabolites between second-hand smoke and CRC. Results:A significant positive causal relationship was observed between exposure to tobacco smoke at home and CRC risk(OR=1.17,95%CI 1.02 to 1.34).However,no significant association was found between exposure to tobacco smoke outside the home and CRC risk(OR=1.07,95%CI 0.95 to 1.20).No evidence of reverse causality was found between home exposure and CRC(P=0.48).Sensitivity analyses indicated no heterogeneity or horizontal pleiotropy.Three blood metabolites,2-palmitoleoyl-GPC(16꞉1),X-24328,and gulonate,showed causal associations with both second-hand smoke exposure and CRC(all P<0.05). Conclusion:Exposure to second-hand smoke at home may causally increase the risk of CRC,and metabolites such as 2-palmitoleoyl-GPC(16꞉1),X-24328,and gulonate may serve as potential mediators in this pathway.关键词
二手烟/结直肠癌/代谢/孟德尔随机化/因果关系Key words
second-hand smoke/colorectal cancer/metabolism/Mendelian randomization/causal relationship引用本文复制引用
张志红,张国飞,王政,杨柳,周兴婷,圣文..基于孟德尔随机化的二手烟与结直肠癌因果关系及代谢物的中介作用[J].临床与病理杂志,2024,44(11):1488-1495,8.基金项目
湖北省卫生健康委科研项目(WJ2023M177).This work was supported by the Health Commission of Hubei Province,China(WJ2023M177). （WJ2023M177）
