Skip to main content
Premium Trial:

Request an Annual Quote

Study Spells Out Smoking-Related DNA Methylation Changes in Lung, Colon Tissue

NEW YORK – By profiling DNA methylation across the genome in samples from nine tissue types, researchers got a look at smoking-related epigenetic changes that arise in lung and colon tissues and explored the predicted gene regulation and expression consequences of these changes.

Past studies, mainly done in leukocyte cells, have hinted that at least some of the health consequences of cigarette smoking may stem from mechanisms involving epigenetic changes, researchers from the University of Chicago, University of Pittsburgh, and the UPMC Hillman Cancer Center explained.

Consequently, the team reasoned that it may uncover additional DNA methylation effects of smoking by systematically profiling a broader set of tissue types using genome-wide DNA methylation profiling — an approach outlined in a paper published in the American Journal of Human Genetics on Thursday.

"If we want to understand the effects of environmental exposures like smoking, it's important to study a variety of tissue types, in addition to blood, because disease occurs in many different organs in the body," senior and corresponding author Brandon Pierce, a public health and human genetics researcher affiliated with the University of Chicago and the UChicago Comprehensive Cancer Center, said in a statement.

Using 916 post-mortem tissue samples collected for the Genotype-Tissue Expression (GTEx) project, the investigators characterized genome-wide cytosine methylation at cytosine-guanine (CpG) dinucleotide sites across the genome in muscle, lung, blood, kidney, breast, prostate, ovary, testis, and colon tissues from donors with documented histories categorizing them as never-smokers, "ever-smokers"— a group including current and former smokers — or current smokers.

The search led to thousands of smoking-related methylation marks centered in two of the tissue types tested, the lung and the colon, which were analyzed in relation to methylation quantitative trait locus data from GTEx, ENCODE annotation clues, and disease-related SNPs previously found in genome-wide association studies.

The genome-wide methylation analyses did not unearth significant smoking-related associations in the remaining tissue types tested.

In the 212 lung tissue samples considered for the study, the team highlighted 6,350 smoking-associated cytosine methylation shifts, many involving lower-than-usual methylation levels. The lung tissue set included 1,646 loci linked to both DNA methylation and local gene expression, the researchers reported.

In the 210 colon tissue samples profiled, meanwhile, they saw more than 2,700 smoking-related methylation changes, and found DNA methylation and gene expression overlap at 22 loci.

But while a handful of loci turned up in both the lung and colon tissue analyses, the team explained, the specific CpG methylation sites involved appeared to be distinct in each of the tissue types, providing tissue-relevant clues to the genes impacted by smoking in the tissues.

"The epigenetic responses to smoking may reflect mechanisms that defend us against or mediate the adverse effects of smoking," co-first author Niyati Jain, a Ph.D. student in public health and genetics, genomics, and systems biology at the University of Chicago, said in a statement. "Characterizing them can give us a better understanding of disease relevance and risk."

In their pathway analyses on smoking-associated DNA methylation changes uncovered in lung tissue, for example, the investigators flagged apoptosis, xenobiotic metabolism, ultraviolet radiation response, cancer-related signaling pathways, and several other impacted pathways.

More generally, Pierce suggested that it may be possible to use a similar strategy to define and track down epigenetic signatures that serve as biomarkers of other environmental exposures.

"The more we can increase the diversity of tissues and number of samples from more people, the more we can learn," he said.