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DNA methylation-based clocks, tobacco smoking, and lung cancer risk
DNA methylation clocks, smoking, and lung cancer risk
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Abstract
Several are positively associated with lung cancer risk, with odds ratios ranging from 1.13 to 1.79.
- DNA methylation clocks such as Hannum, PhenoAge, DunedinPACE, and PCGrimAge show varying degrees of association with lung cancer risk.
- Tobacco smoking explains a modest proportion of variance in most DNAm clocks, but accounts for approximately 30% of variance in the PCGrimAge clock.
- Detailed adjustments for smoking reduced the PCGrimAge association with lung cancer risk by 13%.
- DNA methylation-predicted packyears is identified as an independent predictor of lung cancer risk.
- The PCGrimAge model demonstrates better risk discrimination compared to the PLCO model, with an area under the curve of 0.72.
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Key numbers
1.79
PCGrimAge Association with Lung Cancer Risk
for lung cancer risk per standard deviation increase in PCGrimAge
30%
Variance Explained by Tobacco Smoking
Proportion of variance in PCGrimAge explained by tobacco smoking
0.72
AUC for PCGrimAge Model
Area under the curve for PCGrimAge model in lung cancer risk prediction