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Methylation-based alcohol consumption scores as prognostic biomarkers in colorectal cancer: insights from a population-based cohort

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with alcohol consumption implicated in its etiology. However, alcohol's prognostic impact on CRC survival is unclear, and self-reported intake is limited by bias. This population-based cohort study evaluated blood DNA...

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Main Authors: Yuan, Tanwei (Author) , Tagscherer, Katrin E. (Author) , Roth, Wilfried (Author) , Bewerunge-Hudler, Melanie (Author) , Brobeil, Alexander (Author) , Kloor, Matthias (Author) , Bläker, Hendrik (Author) , Brenner, Hermann (Author) , Hoffmeister, Michael (Author)
Format: Article (Journal)
Language:English
Published: 15 December 2025
In: International journal of cancer
Year: 2025, Volume: 157, Issue: 12, Pages: 2521-2531
ISSN:1097-0215
DOI:10.1002/ijc.70086
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ijc.70086
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.70086
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Author Notes:Tanwei Yuan, Katrin E. Tagscherer, Wilfried Roth, Melanie Bewerunge-Hudler, Alexander Brobeil, Matthias Kloor, Hendrik Bläker, Hermann Brenner, Michael Hoffmeister
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Summary:Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with alcohol consumption implicated in its etiology. However, alcohol's prognostic impact on CRC survival is unclear, and self-reported intake is limited by bias. This population-based cohort study evaluated blood DNA methylation-based alcohol scores as objective prognostic tools in 2,129 CRC patients from Germany's DACHS study (2003-2021; median follow-up: 10 years). Participants were recruited from 22 hospitals in Southwest Germany, including non-metastatic (n = 1757) and metastatic (n = 372) patients with complete methylation and alcohol data. All three assessed methylation scores (3-CpG, 450-CpG, 144-CpG) correlated with self-reported lifetime/recent alcohol intake (Spearman's r: 0.29-0.36; p < 0.0001), particularly recent consumption. In non-metastatic patients, self-reported alcohol consumption showed a J-shaped mortality risk, with elevated risks in heavy drinkers and abstainers. A similar dose-response pattern was observed for the 3-CpG methylation score, which showed consistent and robust associations with increased overall mortality (adjusted hazard ratio [aHR] per standard deviation increase: 1.18, 95% CI: 1.11-1.25), non-CRC-related mortality (1.22, 1.13-1.32), and CRC-specific mortality (1.12, 1.00-1.25). The 450-CpG score was associated with overall mortality (1.07, 1.00-1.15), non-CRC-related mortality (1.14, 1.05-1.23), and alcohol consumption-related mortality (1.59, 1.17-2.16). These findings highlight the potential utility of DNA methylation-based alcohol scores, especially the 3-CpG and the 450-CpG scores, as prognostic tools for CRC outcomes. Such biomarkers may provide a more objective measure of alcohol exposure and complement self-reported data in risk stratification and clinical decision-making, though further validation is warranted before clinical implementation.
Item Description:Zuerst veröffentlicht: 19. August 2025
Gesehen am 15.01.2026
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.70086

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