Dataset Information

Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example.

ABSTRACT: Childhood stressors including physical abuse predict adult cancer risk. Prior research portrays this finding as an indirect mechanism that operates through coping behaviors, including adult smoking, or through increased toxic exposures during childhood. Little is known about potential direct causal mechanisms between early-life stressors and adult cancer. Because prenatal conditions can affect gene expression by altering DNA methylation, with implications for adult health, we hypothesize that maternal stress may program methylation of cancer-linked genes during gametogenesis. To illustrate this hypothesis, we related maternal social resources to methylation at the imprinted MEG3 differentially methylated regulatory region, which has been linked to multiple cancer types. Mothers (n = 489) from a diverse birth cohort (Durham, North Carolina) provided newborns' cord blood and completed a questionnaire. Newborns of currently married mothers showed lower (-0.321 SD, p < .05) methylation compared to newborns of never-married mothers, who did not differ from newborns whose mothers were cohabiting and others (adjusted for demographics). MEG3 DNA methylation levels were also lower when maternal grandmothers co-resided before pregnancy (-0.314 SD, p < .05). A 1-SD increase in prenatal neighborhood disadvantage also predicted higher methylation (-0.137 SD, p < .05). In conclusion, we found that maternal social resources may result in differential methylation of MEG3, which demonstrates a potential partial mechanism priming socially disadvantaged newborns for later risk of some cancers.

SUBMITTER: King KE

PROVIDER: S-EPMC4851425 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example.

King Katherine E KE Kane Jennifer B JB Scarbrough Peter P Hoyo Cathrine C Murphy Susan K SK

Biodemography and social biology 20160101 1

Childhood stressors including physical abuse predict adult cancer risk. Prior research portrays this finding as an indirect mechanism that operates through coping behaviors, including adult smoking, or through increased toxic exposures during childhood. Little is known about potential direct causal mechanisms between early-life stressors and adult cancer. Because prenatal conditions can affect gene expression by altering DNA methylation, with implications for adult health, we hypothesize that ma ...[more]

PMID: 27050035

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Project description:The serotonin transporter gene (5-HTT/SLC6A4)-linked polymorphic region has been suggested to have a modulatory role in mediating effects of early-life stress exposure on psychopathology rendering carriers of the low-expression short (s)-variant more vulnerable to environmental adversity in later life. The underlying molecular mechanisms of this gene-by-environment interaction are not well understood, but epigenetic regulation including differential DNA methylation has been postulated to have a critical role. Recently, we used a maternal restraint stress paradigm of prenatal stress (PS) in 5-HTT-deficient mice and showed that the effects on behavior and gene expression were particularly marked in the hippocampus of female 5-Htt+/- offspring. Here, we examined to which extent these effects are mediated by differential methylation of DNA. For this purpose, we performed a genome-wide hippocampal DNA methylation screening using methylated-DNA immunoprecipitation (MeDIP) on Affymetrix GeneChip Mouse Promoter 1.0?R arrays. Using hippocampal DNA from the same mice as assessed before enabled us to correlate gene-specific DNA methylation, mRNA expression and behavior. We found that 5-Htt genotype, PS and their interaction differentially affected the DNA methylation signature of numerous genes, a subset of which showed overlap with the expression profiles of the corresponding transcripts. For example, a differentially methylated region in the gene encoding myelin basic protein (Mbp) was associated with its expression in a 5-Htt-, PS- and 5-Htt × PS-dependent manner. Subsequent fine-mapping of this Mbp locus linked the methylation status of two specific CpG sites to Mbp expression and anxiety-related behavior. In conclusion, hippocampal DNA methylation patterns and expression profiles of female prenatally stressed 5-Htt+/- mice suggest that distinct molecular mechanisms, some of which are promoter methylation-dependent, contribute to the behavioral effects of the 5-Htt genotype, PS exposure and their interaction.

Dataset Information

Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example.

Publications

Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example.

Similar Datasets

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