Genomic DNA Methylation among Women in a Multiethnic New York City Birth Cohort

Terry, Mary Beth; Ferris, Jennifer S.; Pilsner, Richard; Flom, Julie D.; Tehranifar, Parisa; Santella, Regina M.; Gamble, Mary V.; Süsser, Ezra

doi:10.1158/1055-9965.epi-08-0312

Cited by 160 publications

(165 citation statements)

References 23 publications

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“…Instead global DNA hypermethylation was observed in children whose mothers smoked during pregnancy. 39 These and our findings are in line with the global hypermethylation found in the sperm of mice exposed for 3 weeks to particulate air pollution of urban/ industrial source, in which PAH exposure was confirmed by the presence of elevated PAH-DNA adduct levels in the mice lungs. 15 Moreover, following in vitro chronic exposure to B[a]P, global DNA hypermethylation was associated to DNMT1 overexpression in mouse embryonic fibroblasts.…”

Section: Discussionsupporting

confidence: 91%

Global and gene‐specific promoter methylation changes are related to anti‐B[a]PDE‐DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon‐exposed individuals

Pavanello

Bollati

Pesatori

et al. 2009

Intl Journal of Cancer

139

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We investigated the effect of chronic exposure to polycyclic aromatic hydrocarbons (PAHs) on DNA methylation states (percentage of methylated cytosines (%mC)) in Polish male nonsmoking coke-oven workers and matched controls. Methylation states of gene-specific promoters (p53, p16, HIC1 and IL-6) and of Alu and LINE-1 repetitive elements, as surrogate measures of global methylation, were quantified by pyrosequencing in peripheral blood lymphocytes (PBLs). DNA methylation was evaluated in relation to PAH exposure, assessed by urinary 1-pyrenol and anti-benzo [a] We found that Alu and LINE-1 methylation levels and those of the inflammatory cytokine IL-6, to a lesser extent, were higher in polycyclic aromatic hydrocarbon (PAH)-exposed coke-oven workers than controls (p < 0.001 and p 5 0.094). Conversely, methylation of p53 and HIC1 tumor suppressors was lower in workers compared with controls (p < 0.001 and p < 0.05). Global and IL-6 hypermethylation and p53 hypomethylation were significantly correlated, not only to PAH-exposure (urinary 1-pyrenol) but also to the anti-B[a]PDE-DNA adduct levels (p < 0.01). Overall, linear multivariate regression analysis showed that the only significant determinant of increasing micronuclei (MN) (p < 0.01) was p53 hypomethylation and not the other LINE-1, Alu, p53, HIC1 and IL-6 methylation states.Gene-specific promoters (mainly p53) and global (Alu and LINE-1 repeats) DNA methylation changes in circulating peripheral blood lymphocytes (PBLs), related to anti-B[a]PDE-DNA adduct and MN, suggest that these events could be determined to identify subjects at high cancer risk.Understanding how environmental factors are involved in cancer etiology and development is one of the main goals of biomedical research. 1 Extensive research has been conducted to determine how known or potential environmental carcinogens modify the DNA sequence, as a component of malignant transformation. However, an investigative approach exclusively based on genetic damage, as well as on inheritance of genetic variants, has been revealed to be insufficient to account for multistage carcinogenic processes. 2 It has been proposed that DNA methylation, one of the best known epigenetic mechanisms, shares critical roles with DNA mutations in the theoretical continuum for exposure to cancer. 3,4 One potential mechanism for environmental factors is through hypermethylation or hypomethylation on somatic cells, leading to activation or silencing of key genes in critical pathways of cancer. 5,6 From some years, the disruption of DNA methylation status by exposure to genotoxic agents has been an issue in the literature, but the clear demonstration that such epigenetic alterations were caused by one or more specific agents in people has been demanding (for a review see Ref. 7 and references therein).Benzo [a]pyrene (B[a]P), the most well-studied PAH carcinogen (especially of the lung), has a well-established genotoxic mechanism, via metabolic activation to diol epoxide. 8 The stereoselective binding of anti-benzo[a]pyrene di...

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Section: Discussionsupporting

confidence: 91%

Global and gene‐specific promoter methylation changes are related to anti‐B[a]PDE‐DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon‐exposed individuals

Pavanello

Bollati

Pesatori

et al. 2009

Intl Journal of Cancer

139

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“…There is a growing body of evidence suggesting that human DNA methylation is responsive to environmental exposures during both intrauterine development and after birth in humans (68)(69)(70)(71)(72)(73).…”

Section: First Studies Of Deep Archeology Of Biological Embedding In mentioning

confidence: 99%

Putting the concept of biological embedding in historical perspective

Hertzman

2012

Proc. Natl. Acad. Sci. U.S.A.

194

164

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This paper describes evidence that led to the concept of biological embedding and research approaches designed to elucidates its mechanisms. Biological embedding occurs when experience gets under the skin and alters human biological and developmental processes; when systematic differences in experience in different social environments in society lead to systematically different biological and developmental states; when these differences are stable and long term; and, finally, when they have the capacity to influence health, well-being, learning, or behavior over the life course. Biological embedding emerged from insights in population health on the unique characteristics of socioeconomic gradients: Ubiquity in poor and postscarcity societies alike; gradient seen regardless of whether socioeconomic status is measured by income, education, or occupation; cutting widely across health, well-being, learning, and behavior outcomes; replicating itself on new conditions entering society; and, often, showing that flatter gradients mean better overall societal outcomes. Most important, the gradient begins the life course as a gradient in developmental health, suggesting that the emergence of a multifaceted resilience/vulnerability early in life is the best place to look for evidence of biological embedding. To understand its character, the metaphor of the “archeology of biological embedding” has been used, wherein the surficial stratum of the “dig” is experience and behavior, the shallow stratum is organ system and cellular function, and the deep stratum is gene function. We are now ready to address the fundamental question of biological embedding: How do early childhood environments work together with genetic variation and epigenetic regulation to generate gradients in health and human development across the life course?

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“…12 To date, however, few studies have examined differential methylation by race in histologically normal tissues. [13][14][15] Among them, analyses have been limited to global methylation and to blood specimens. 13,14 In one study to examine genomewide methylation differences by race, Adkins et al reported 3,623 loci in DNA significant differentially methylated between AAs and EAs at birth using umbilical cord blood.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15] Among them, analyses have been limited to global methylation and to blood specimens. 13,14 In one study to examine genomewide methylation differences by race, Adkins et al reported 3,623 loci in DNA significant differentially methylated between AAs and EAs at birth using umbilical cord blood. 15 However, to our knowledge, no study has comprehensively examined differences in methylation by race of genome-wide DNA methylation in normal breast tissues.…”

Section: Introductionmentioning

confidence: 99%

Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women

et al. 2015

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Breast cancer is more common in European Americans (EAs) than in African Americans (AAs) but mortality from breast cancer is higher among AAs. While there are racial differences in DNA methylation and gene expression in breast tumors, little is known whether such racial differences exist in breast tissues of healthy women. Genome-wide DNA methylation and gene expression profiling was performed in histologically normal breast tissues of healthy women. Linear regression models were used to identify differentially-methylated CpG sites (CpGs) between EAs (n D 61) and AAs (n D 22). Correlations for methylation and expression were assessed. Biological functions of the differentially-methylated genes were assigned using the Ingenuity Pathway Analysis. Among 485 differentially-methylated CpGs by race, 203 were hypermethylated in EAs, and 282 were hypermethylated in AAs. Promoter-related differentially-methylated CpGs were more frequently hypermethylated in EAs (52%) than AAs (27%) while gene body and intergenic CpGs were more frequently hypermethylated in AAs. The differentially-methylated CpGs were enriched for cancer-associated genes with roles in cell death and survival, cellular development, and cell-to-cell signaling. In a separate analysis for correlation in EAs and AAs, different patterns of correlation were found between EAs and AAs. The correlated genes showed different biological networks between EAs and AAs; networks were connected by Ubiquitin C. To our knowledge, this is the first comprehensive genome-wide study to identify differences in methylation and gene expression between EAs and AAs in breast tissues from healthy women. These findings may provide further insights regarding the contribution of epigenetic differences to racial disparities in breast cancer.

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Genomic DNA Methylation among Women in a Multiethnic New York City Birth Cohort

Cited by 160 publications

References 23 publications

Global and gene‐specific promoter methylation changes are related to anti‐B[a]PDE‐DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon‐exposed individuals

Global and gene‐specific promoter methylation changes are related to anti‐B[a]PDE‐DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon‐exposed individuals

Putting the concept of biological embedding in historical perspective

Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women

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