Academic Journal
Exploring the cross-cancer effect of smoking and its fingerprints in blood DNA methylation on multiple cancers:A Mendelian randomization study
| العنوان: | Exploring the cross-cancer effect of smoking and its fingerprints in blood DNA methylation on multiple cancers:A Mendelian randomization study |
|---|---|
| المؤلفون: | Zhou, Yajing, Zhou, Xuan, Sun, Jing, Wang, Lijuan, Zhao, Jianhui, Chen, Jie, Yuan, Shuai, He, Yazhou, Timofeeva, Maria, Spiliopoulou, Athina, Mesa-Eguiagaray, Ines, Farrington, Susan M., Ding, Kefeng, Dunlop, Malcolm G., Qian, Xiao, Theodoratou, Evropi, Li, Xue |
| المصدر: | Zhou , Y , Zhou , X , Sun , J , Wang , L , Zhao , J , Chen , J , Yuan , S , He , Y , Timofeeva , M , Spiliopoulou , A , Mesa-Eguiagaray , I , Farrington , S M , Ding , K , Dunlop , M G , Qian , X , Theodoratou , E & Li , X 2023 , ' Exploring the cross-cancer effect of smoking and its fingerprints in blood DNA methylation on multiple cancers : A Mendelian randomization study ' , International Journal of Cancer .... |
| سنة النشر: | 2023 |
| المجموعة: | University of Southern Denmark: Research Output / Syddansk Universitet |
| مصطلحات موضوعية: | cross-cancer effect, DNA methylation, Mendelian randomization, methylation quantitative trait loci, smoking, Genome-Wide Association Study, Humans, CpG Islands/genetics, Smoking/adverse effects, Mendelian Randomization Analysis, Female, Neoplasms/epidemiology |
| الوصف: | Aberrant smoking-related DNA methylation has been widely investigated as a carcinogenesis mechanism, but whether the cross-cancer epigenetic pathways exist remains unclear. We conducted two-sample Mendelian randomization (MR) analyses respectively on smoking behaviors (age of smoking initiation, smoking initiation, smoking cessation, and lifetime smoking index [LSI]) and smoking-related DNA methylation to investigate their effect on 15 site-specific cancers, based on a genome-wide association study (GWAS) of 1.2 million European individuals and an epigenome-WAS (EWAS) of 5907 blood samples of Europeans for smoking and 15 GWASs of European ancestry for multiple site-specific cancers. Significantly identified CpG sites were further used for colocalization analysis, and those with cross-cancer effect were validated by overlapping with tissue-specific eQTLs. In the genomic MR, smoking measurements of smoking initiation, smoking cessation and LSI were suggested to be casually associated with risk of seven types of site-specific cancers, among which cancers at lung, cervix and colorectum were provided with strong evidence. In the epigenetic MR, methylation at 75 CpG sites were reported to be significantly associated with increased risks of multiple cancers. Eight out of 75 CpG sites were observed with cross-cancer effect, among which cg06639488 (EFNA1), cg12101586 (CYP1A1) and cg14142171 (HLA-L) were validated by eQTLs at specific cancer sites, and cg07932199 (ATXN2) had strong evidence to be associated with cancers of lung (coefficient, 0.65, 95% confidence interval [CI], 0.31-1.00), colorectum (0.90 [0.61, 1.18]), breast (0.31 [0.20, 0.43]) and endometrium (0.98 [0.68, 1.27]). These findings highlight the potential practices targeting DNA methylation-involved cross-cancer pathways. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1002/ijc.34656 |
| الاتاحة: | https://portal.findresearcher.sdu.dk/da/publications/a1e8b656-8023-49e1-8f8f-2d832c257aaf https://doi.org/10.1002/ijc.34656 https://findresearcher.sdu.dk/ws/files/254742422/Intl_Journal_of_Cancer_-_2023_-_Zhou_-_Exploring_the_cross_cancer_effect_of_smoking_and_its_fingerprints_in_blood_DNA.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.51F07FA3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/ijc.34656 |
|---|