Ji, XinyuLin, LijuanFan, JuanjuanLi, YiWei, YongyueShen, SipengSu, LiShafer, AndreaBjaanaes, Maria MoksnesKarlsson, AnnaPlanck, MariaStaaf, JohanHelland, ÅslaugEsteller, Manel, 1968-Zhang, RuyangChen, FengChristiani, David C.2025-05-222025-05-222021-12-211574-7891https://hdl.handle.net/2445/221180The interaction between DNA methylation of tripartite motif containing 27 (cg05293407TRIM27 ) and smoking has previously been identified to reveal histologically heterogeneous effects of TRIM27 DNA methylation on early-stage non-small cell lung cancer (NSCLC) survival. However, to understand the complex mechanisms underlying NSCLC progression, we searched three-way interactions. A two-phase study was adopted to identify three-way interactions in the form of pack-year of smoking (number of cigarettes smoked per day × number of years smoked) × cg05293407TRIM27 × epigenome-wide DNA methylation CpG probe. Two CpG probes were identified with FDR-q≤0.05 in the discovery phase and P≤0.05 in the validation phase: cg00060500KIAA0226 and cg17479956EXT2 . Compared to a prediction model with only clinical information, the model added 42 significant three-way interactions using a looser criterion (discovery: FDR-q≤0.10, validation: P≤0.05), had substantially improved the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model for both 3-year and 5-year survival. Our research identified the complex interaction effects among multiple environment and epigenetic factors, and provided therapeutic target for NSCLC patients.15 p.application/pdfengcc-by (c) Ji, X. et al., 2021http://creativecommons.org/licenses/by/4.0/AutofàgiaADNEpigènesiCarcinogènesiAutophagyDNAEpigenesisCarcinogenesisinfo:eu-repo/semantics/article7171322025-05-22info:eu-repo/semantics/openAccess34932879