Using Cg05575921 methylation to predict lung cancer risk: a potentially bias-free precision epigenetics approach.

The decision to engage in lung cancer screening (LCS) necessitates weighing benefits versus harms. Previously, clinicians in the United States have used the PLCOM2012 algorithm to guide LCS decision-making. However, that formula contains race and gender-based variables. Previously, using data from a European study, Bojesen and colleagues have suggested that cg05575921 methylation could guide decision-making. To test this hypothesis in a more diverse American population, we examined DNA and clinical data from 3081 subjects from the National Lung Screening Trial (NLST) study. Using survival analysis, we found a simple linear predictor consisting of age, pack-year consumption and cg05575921, to have the best predictive power among several alternatives (AUC = 0.66). Results showed that the highest quartile of risk was more than 2-fold more likely to develop lung cancer than those in the lowest quartile. Race, ethnicity, and gender had no effect on prediction with both cg05575921 and pack years contributing equally (both p < 0.003) to risk prediction. Current smokers had considerably lower methylation than former smokers (46% vs 67%; p < 0.001) with the average methylation of those who quit approaching 80% after 25 years of cessation. Finally, current male smokers had lower mean cg05575921 percentage than female smokers (46% vs 49%; p < 0.001). We conclude that cg05575921 (along with age and pack years) can be used to guide LCS decision-making, and additional studies might focus on how best to use methylation to inform decision-making.

Cost-utility analysis of an integrated genetic/epigenetic test for assessing risk for coronary heart disease.

Aim: New epigenetically based methods for assessing risk for coronary heart disease may be more sensitive but are generally more costly than current methods. To understand their potential impact on healthcare spending, we conducted a cost-utility analysis. Methods: We compared costs using the new Epi + Gen CHD™ test with those of existing tests using a cohort Markov simulation model. Results: We found that use of the new test was associated with both better survival and highly competitive negative incremental cost-effectiveness ratios ranging from -$42,000 to -$8000 per quality-adjusted life year for models with and without a secondary test. Conclusion: The new integrated genetic/epigenetic test will save money and lives under most real-world scenarios. Similar advantages may be seen for other epigenetic tests.