Détail du document
Identifiant
doi:10.1038/s41416-023-02397-6...
Auteur
Zhou, Xuan Xiao, Qian Jiang, Fangyuan Sun, Jing Wang, Lijuan Yu, Lili Zhou, Yajing Zhao, Jianhui Zhang, Han Yuan, Shuai Timofeeva, Maria Spiliopoulou, Athina Mesa-Eguiagaray, Ines Farrington, Susan M. Law, Philip J. Houlston, Richard S. Ding, Kefeng Dunlop, Malcolm G. Theodoratou, Evropi Li, XueLangue
enEditeur
Nature
Catégorie
Epidemiology
Année
2023
Date de référencement
23/08/2023
Mots clés
colorectal dna tobacco cancer evidence risk analyses crc smokingRésumé
Background Tobacco smoking is suggested as a risk factor for colorectal cancer (CRC), but the complex relationship and the potential pathway are not fully understood.
Methods We performed two-sample Mendelian randomisation (MR) analyses with genetic instruments for smoking behaviours and related DNA methylation in blood and summary-level GWAS data of colorectal cancer to disentangle the relationship.
Colocalization analyses and prospective gene-environment interaction analyses were also conducted as replication.
Results Convincing evidence was identified for the pathogenic effect of smoking initiation on CRC risk and suggestive evidence was observed for the protective effect of smoking cessation in the univariable MR analyses.
Multivariable MR analysis revealed that these associations were independent of other smoking phenotypes and alcohol drinking.
Genetically predicted methylation at CpG site cg17823346 [ ZMIZ1 ] were identified to decrease CRC risk; while genetically predicted methylation at cg02149899 would increase CRC risk.
Colocalization and gene-environment interaction analyses added further evidence to the relationship between epigenetic modification at cg17823346 [ ZMIZ1 ] as well as cg02149899 and CRC risk.
Discussion Our study confirms the significant association between tobacco smoking, DNA methylation and CRC risk and yields a novel insight into the pathogenic effect of tobacco smoking on CRC risk.
Zhou, Xuan,Xiao, Qian,Jiang, Fangyuan,Sun, Jing,Wang, Lijuan,Yu, Lili,Zhou, Yajing,Zhao, Jianhui,Zhang, Han,Yuan, Shuai,Timofeeva, Maria,Spiliopoulou, Athina,Mesa-Eguiagaray, Ines,Farrington, Susan M.,Law, Philip J.,Houlston, Richard S.,Ding, Kefeng,Dunlop, Malcolm G.,Theodoratou, Evropi,Li, Xue, 2023, Dissecting the pathogenic effects of smoking and its hallmarks in blood DNA methylation on colorectal cancer risk, Nature
