Prenatal Tobacco Smoke Exposure and Genomewide Methylation in Adulthood

Abstract

Abstract Genomic DNA demethylation, including demethylation of repetitive elements (which comprise 45% of the human genome), has been linked to increased risk of breast and other cancers. Genomic DNA methylation can be altered prenatally and throughout life and may be a mechanism through which the environment alters disease risk. There is evidence that prenatal tobacco smoke exposure has a persistent impact on genomic DNA methylation; however, no study to date has assessed the association between prenatal smoke exposure and adult repetitive element methylation. We measured repetitive element methylation of Alu, LINE-1, and Sat2 using MethyLight in 92 members of the New York Women's Birth Cohort, a follow-up of former female participants of the New York site of the U.S. National Collaborative Perinatal Project (mean age at blood draw = 43.5, SD = 1.8). Prenatal smoke exposure was reported prospectively. We estimated associations using multivariable linear regression, and used the natural log of Alu, LINE-1, and Sat2 methylation level. Thirty-one (36%) participants were exposed to prenatal smoke. These participants were more likely to smoke at the time of interview (P < 0.01). Prenatal smoke exposure was inversely associated with genomic DNA methylation of Sat2 and Alu, adjusted for age, childhood environmental tobacco smoke exposure (ETS) and adult smoking status (exposed vs. unexposed to prenatal smoke: Sat2: β = −0.20, 95% CI = −0.39, −0.02; Alu: β = −0.09, 95% CI = −0.26, 0.08). In multivariable models, childhood ETS had a positive, borderline significant association with Sat2 methylation (β = 0.17, 95% CI −0.02, 0.37). If replicated in larger studies, these results suggest that prenatal smoke exposure may have a persistent impact on genomic DNA demethylation of Sat2 and Alu in adulthood, and thus may be a pathway through which prenatal smoke exposure impacts adult disease. Results are strengthened by the fact that prenatal smoke exposure data were collected prospectively in the early 1960s, before there was a stigma associated with maternal smoking during pregnancy. These results are consistent with the one study assessing this relation in children. Further studies are needed to confirm this finding and to investigate the underlying biological mechanism.