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Updated: Jun 8, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Blood-based DNA methylation marker model for short-term and long-term lung cancer risk prediction
Megha Bhardwaj1,2, Yi-Qian Sun3,4,5, Clara Frick6,7
1Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center (DKFZ), Heidelberg, Germany. megha.bhardwaj@dkfz-heidelberg.de.
Background:
Screening heavy smokers with low-dose computed tomography (LDCT) has been shown to reduce lung cancer (LC) mortality, however, identifying the specific high-risk population that benefits most, a critical requirement for implementing effective and cost-efficient screening, remains challenging.
Methods:
We developed and validated a blood-based DNA methylation marker model (BBDMM) for all participants, including both ever and never smokers, using the LC risk-informative CpG sites from epigenome-wide association studies (EWAS). The model was developed and internally validated in 2,459 participants from ESTHER, a population-based cohort from Germany. Subsequently, BBDMM was externally validated in exactly same 233 participants drawn from the Norwegian HUNT2 and HUNT3 cohorts with long- and short-term follow-ups and cases identified up to 18 and 6.7 years before LC diagnosis, respectively.
Results:
The BBDMM predicted LC incidence with an area under the curve (AUC) of 0.84 [95% confidence interval (95% CI), 0.80-0.87] in the derivation set. In the independent external validation sets, AUCs of 0.85 (95% CI, 0.80-0.90) and 0.85 (95% CI, 0.80-0.90) were observed in HUNT2 and HUNT3, respectively.
Conclusions:
The BBDMM identified future lung cancer cases with promising potential and the model discrimination was highly stable at different time points. These markers may contribute to the evolution of a blood-based test for predicting LC risk.
