%0 Journal Article %A Yuan, Tanwei %A Tagscherer, Katrin E %A Roth, Wilfried %A Bewerunge-Hudler, Melanie %A Brobeil, Alexander %A Kloor, Matthias %A Bläker, Hendrik %A Brenner, Hermann %A Hoffmeister, Michael %T Methylation-based smoking signatures in blood and tissue samples for the prediction of self-reported smoking status and mortality in patients with colorectal cancer. %J Clinical epigenetics %V 17 %N 1 %@ 1868-7075 %C [Erscheinungsort nicht ermittelbar] %I BioMed Central %M DKFZ-2025-01350 %P 113 %D 2025 %Z #EA:C070#LA:C070# %X Smoking is a well-established risk factor for colorectal cancer (CRC) development. However, the reliability of DNA methylation-based smoking signatures in predicting smoking status and their prognostic value in CRC remain unclear, particularly across different biological sample types.Five previously validated methylation-based smoking signatures were analyzed in 2237 CRC patients with blood-derived DNA and 2273 patients with tumor tissue-derived DNA. Blood-derived signatures showed strong correlations with self-reported smoking status, effectively differentiating current smokers from never smokers (all p < 0.0001), with excellent discriminative ability (median area under the receiver operating characteristic curve: 0.94). In contrast, tumor tissue-derived signatures exhibited much weaker associations with smoking status. Among non-metastatic CRC patients, blood-derived methylation signatures were significantly associated with increased risks of all-cause and non-CRC-related mortality, but not with CRC-specific mortality. Conversely, two tumor tissue-derived signatures demonstrated stronger associations with CRC-specific mortality compared to blood-derived signatures.Blood-derived methylation-based smoking signatures are robust indicators for smoking exposure and are associated with increased mortality risk among non-metastatic CRC patients. When applied to tumor tissue, signatures showed stronger associations with CRC-specific mortality. %K Humans %K Colorectal Neoplasms: genetics %K Colorectal Neoplasms: mortality %K Colorectal Neoplasms: blood %K DNA Methylation %K Male %K Female %K Middle Aged %K Smoking: genetics %K Smoking: adverse effects %K Smoking: blood %K Self Report %K Aged %K Prognosis %K Risk Factors %K Colorectal cancer (Other) %K DNA methylation biomarkers (Other) %K Prognosis (Other) %K Smoking (Other) %F PUB:(DE-HGF)16 %9 Journal Article %$ pmid:40611182 %2 pmc:PMC12225191 %R 10.1186/s13148-025-01918-9 %U https://inrepo02.dkfz.de/record/302810