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Updated: May 2, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
A DNA Methylation Marker, cg05575921 (AHRR), Outperforms Self-Reported Smoking Exposure for Its Association With
Gregory T Jones1, Michael J A Williams2, Manar Khashram3
1Department of Surgical Sciences, Dunedin Medical School, University of Otago, Dunedin, New Zealand.
DNA methylation at AHRR cg05575921 accurately identifies smoking status and predicts cardiovascular disease (CVD) prevalence. This epigenetic marker offers stronger CVD prediction than self-reports, potentially improving risk scores.
Area of Science:
- Epigenetics
- Cardiovascular Disease Research
- Smoking Cessation Biomarkers
Background:
- Differential DNA methylation (DNAm) at the AHRR gene (CpG site cg05575921) is a validated biomarker for tobacco smoking exposure.
- Previous research established cg05575921 DNAm as a reliable indicator of smoking status.
Purpose of the Study:
- To investigate the clinical relevance of AHRR cg05575921 DNAm in relation to prevalent cardiovascular disease (CVD).
- To compare the predictive performance of this DNAm marker against traditional self-reported smoking assessments for CVD risk.
Main Methods:
- Assessed whole blood cg05575921 (AHRR) DNAm using droplet digital PCR in a cohort of 2784 elderly individuals.
- Utilized DNAm values to impute smoking status and analyze its independent association with prevalent CVD.
Main Results:
- cg05575921 DNAm demonstrated significant accuracy in identifying smoking status (never, ex-, current) and duration of cessation.
- DNAm-imputed smoking status showed a significant non-linear association with prevalent CVD, independent of self-reported smoking status and other covariates.
- Elevated cg05575921 levels were significantly associated with CVD even in never-smokers.
Conclusions:
- Imputed smoking status based on AHRR cg05575921 DNAm is significantly and independently associated with CVD prevalence.
- This epigenetic marker demonstrates superior predictive performance for CVD compared to self-reported smoking assessments.
- The findings suggest potential clinical utility of cg05575921 DNAm for enhancing precision medicine approaches in chronic disease risk prediction.
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