Comparative Analysis of Smoking-Induced DNA Methylation in Blood versus Lung

Undergraduate #97
Discipline: Biological Sciences
Subcategory: Genetics

Joshua Dawson - University of Washington
Co-Author(s): Mullen, Daniel J.; Laird-Offringa, Ite A.; University of Southern California, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California

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Lung cancer is the leading cause of cancer-related death in both men and women in the United States. Smoking is the major cause of lung cancer. While tobacco smoke is well-known to cause mutations in DNA that drive the cancerous phenotype, it also causes epigenetic changes – changes in the regulatory information overlaid on the genome. Smoking has been shown in numerous epidemiological studies of subjects’ whole blood to affect an epigenetic mark called DNA methylation. DNA methylation consists of a methyl group added to cytosine in the context of a CpG dinucleotide. Hypomethylation at several CpGs in the blood has been shown to predict lung cancer risk. The mechanism by which DNA methylation changes in blood are linked to cancer in the lung are poorly understood. To figure this out, I used R to collect CpGs that are statistically significantly differentially methylated in smokers’ versus non-smokers’ whole blood. I analyzed 18 published peer-reviewed articles and collected 20,946 uniquely differentially methylated CpGs. I then utilized the UCSC Genome Browser and The Cancer Genome Atlas (TCGA) data to compare smoking-induced methylation changes in whole blood with those of non-tumor lung tissue and lung adenocarcinoma. Understanding the relationship between whole blood methylation and lung methylation can reveal if blood DNA methylation patterns are good surrogate markers for DNA methylation that occurs in the lung. Further studies of select differentially methylated lung CpGs can help unravel the mechanism by which smoking-induced epigenetic changes contribute to lung cancer development.

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Funder Acknowledgement(s): Bridging the Gaps Summer Program

Faculty Advisor: Ite Laird-Offringa, ilaird@usc.edu

Role: I used 'R' to analyze changes in DNA methylation levels between smokers and non-smokers in the lung across 18 peer-reviewed articles. After identifying the statistically significantly differentially methylated CpGs between smokers and non-smokers in the blood, I utilized The Cancer Genome Atlas and UCSC Genome Browser to compare DNA methylation level changes between smokers and non-smokers in the lung. Lastly, I identified overlap of statistically significantly differentially methylated CpGs in the blood and lung between smokers and non-smokers to identify possible surrogate markers for lung cancer susceptibility.