Synergic effect of arsenic exposure related methylation changes in three cohorts exposed to levels of this toxicant.

PURPOSE

The results of studies assessing impact of arsenic exposure on methylome are to large extent inconsistent. To contribute to understanding of effect of arsenic exposure on methylome of the exposed cells, we assess the impact of low-level arsenic exposure on methylome of blood cells in three cohorts of exposed individuals.

METHODS

The Infinium MethylationEPIC array (Illumina Inc.) was used for genome-wide methylation profiling and robust linear regression to identify arsenic-related methylation changes in blood cells from healthy individuals with a 12-year cancer-free follow-up and breast cancer patients, sampled on average 4.29 years before diagnosis, as well as methylomics data from cord blood samples of Biomarkers of Exposure to Arsenic cohort.

RESULTS

Our analysis identified a 2,453 arsenic-associated methylation changes in blood from healthy individuals, 9,662 in breast cancer patients and 6,745 in cord blood samples. Similarly to previous studies methylation changes that we identified in each cohort, overlapped only to some extent. However, molecular processes linked to identified methylation changes were very similar in each of the cohorts. And included pathways that could be clearly associated with the adverse effects of arsenic exposure and specifically cancer in the cohort of cancer patients. Moreover, the genomic regions harboring identified in each cohort methylation changes were similar and predominantly included regions participating in regulation of gene transcription.

CONCLUSION

Overall, our findings show that specificity of arsenic related methylation changes is low but the impact of these changes on cell physiology is very similar across three cohorts we studded.