Sex-specific associations of arsenic exposure with global DNA methylation and hydroxymethylation in leukocytes: Results from two studies in Bangladesh

Megan M. Niedzwiecki, Xinhua Liu, Megan N. Hall, Tiffany Thomas, Vesna Slavkovich, Vesna Ilievski, Diane Levy, Shafiul Alam, Abu B. Siddique, Faruque Parvez, Joseph H. Graziano, Mary V. Gamble

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Background: Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)-a class I human carcinogen linked to skin lesion and cancer risk-is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hmC has not been widely studied. Methods: We evaluated associations of As in drinking water, urine, and blood with global %5-mC and %5-hmC in two studies of Bangladeshi adults: (i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity study (n=196; 49% male, 19-66 years); and (ii) peripheral blood mononuclear cell DNA in the Folate and Oxidative Stress study (n=375; 49% male, 30-63 years). Results: Overall, As was not associated with global %5-mC or %5-hmC. Sex-specific analyses showed that associations of As exposure with global %5-hmC were positive in males and negative in females (P for interaction < 0.01). Analyses examining interactions by elevated plasma total homocysteine (tHcys), an indicator of B-Vitamin Deficiency, found that tHcys also modified the association between As and global %5-hmC (P for interaction < 0.10). Conclusion: In two samples, we observed associations between As exposure and global %5-hmC in blood DNA that were modified by sex and tHcys. Impact: Our findings suggest that As induces sex-specific changes in 5-hmC, an epigenetic mark that has been associated with cancer. Future research should explore whether altered %5-hmC is a mechanism underlying the sex-specific influences of As on skin lesion and cancer outcomes.

Original languageEnglish
Pages (from-to)1748-1757
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number11
DOIs
StatePublished - Nov 2015

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