Aim: The expression level of DNA repair-related genes and their association with breast cancer status among participants of the New York site of the Breast Cancer Family Registry was investigated.
Materials And Methods: RNA from mononuclear cells in 194 sister sets (n=475 women) were assayed for ATM, BRCA1, MSH2, MUTYH and XPC gene expression levels and analyzed using generalized estimating equations (GEE).
Results: Individuals with decreased ATM and MSH2 expression had significantly higher odds for breast cancer compared to individuals with higher levels of expression (odds ratio (OR)=1.
While the developing fetus is largely shielded from the external environment through the protective barrier provided by the placenta, it is increasingly appreciated that environmental agents are able to cross and even accumulate in this vital organ for fetal development. To examine the potential influence of environmental pollutants on the placenta, we assessed the relationship between polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and several epigenetic marks linked to fetoplacental development. We measured / imprint control region methylation, and expression, loss of imprinting (LOI) and global DNA methylation levels in placenta ( = 116) collected in a formative research project of the National Children's Study to explore the relationship between these epigenetic marks and the selected organic environmental pollutants.
View Article and Find Full Text PDFThe placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas.
View Article and Find Full Text PDFThe importance of imprinted genes in regulating feto-placental development has been long established. However, a comprehensive assessment of the role of placental imprinted gene expression on fetal growth has yet to be conducted. In this study, we examined the association between the placental expression of 108 established and putative imprinted genes and birth weight in 677 term pregnancies, oversampled for small for gestational age (SGA) and large for gestational age (LGA) infants.
View Article and Find Full Text PDFMany epidemiologic studies of environmental exposures and disease susceptibility measure DNA methylation in white blood cells (WBC). Some studies are also starting to use saliva DNA as it is usually more readily available in large epidemiologic studies. However, little is known about the correlation of methylation between WBC and saliva DNA.
View Article and Find Full Text PDFMature microRNAs (miRNAs) are a class of small non-coding RNAs involved in posttranslational gene silencing. Previous studies found that downregulation of miRNAs is a common feature observed in solid tumors, including hepatocellular carcinoma (HCC). We employed a genome-wide approach to test the hypothesis that DNA methylation alterations in miRNA host genes may cause deregulated miRNA expression in HCC.
View Article and Find Full Text PDFLower global DNA methylation is associated with genomic instability and it is one of the epigenetic mechanisms relevant to carcinogenesis. Emerging evidence for several cancers suggests that lower overall levels of global DNA methylation in blood are associated with different cancer types, although less is known about breast cancer. We examined global DNA methylation levels using a sibling design in 273 sisters affected with breast cancer and 335 unaffected sisters from the New York site of the Breast Cancer Family Registry.
View Article and Find Full Text PDFAltered levels of global DNA methylation and gene silencing through methylation of promoter regions can impact cancer risk, but little is known about their environmental determinants. We examined the association between lifestyle factors and levels of global genomic methylation and IL-6 promoter methylation in white blood cell DNA of 165 cancer-free subjects, 18-78 years old, enrolled in the COMIR (Commuting Mode and Inflammatory Response) study, New York, 2009-2010. Besides self-administrated questionnaires on diet and physical activity, we measured weight and height, white blood cell (WBC) counts, plasma levels of high sensitivity C-reactive protein (hs-CRP), and genomic (LINE-1) and gene-specific methylation (IL-6) by pyrosequencing in peripheral blood WBC.
View Article and Find Full Text PDFBackground And Aims: Commuting by public transportation (PT) entails more physical activity and energy expenditure than by cars, but its biologic consequences are unknown.
Methods: In 2009-2010, we randomly sampled New York adults, usually commuting either by car (n=79) or PT (n=101). Measures comprised diet and physical activity questionnaires, weight and height, white blood cell (WBC) count, C reactive protein, (CRP) gene-specific methylation (IL-6), and global genomic DNA methylation (LINE-1 methylation).
The peroxynitrite-mediated activation of matrix metalloproteinase-2 (MMP-2) and subsequent cleavage of troponin I (TnI) in ventricular myocytes is a detrimental effect of ischemia/reperfusion injury. We hypothesized that acetaminophen, an effective antioxidant against peroxynitrite, would attenuate activation of MMP-2 and improve cardiac mechanical function. Isolated, perfused guinea pig hearts (Langendorff) were treated with either acetaminophen [0.
View Article and Find Full Text PDFTissue inhibitor of metalloproteinases-1 (TIMP-1) is a widely expressed, secreted protein that functions primarily to inhibit members of a large family of metalloproteinases (MPs). Because of the ability of TIMP-1 to inhibit MPs, it functions in many of the same pathophysiological processes as these enzymes, e.g.
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