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Project description:Background: Low socioeconomic status (SES) has been linked to chronic stress and poorer health outcomes for marginalized communities in the U.S. The biological processes mediating the impact of SES on health to promote chronic diseases, such as cancer, remain poorly understood. Here, we aim to determine how changes in DNA methylation are linked to neighborhood-level socioeconomic deprivation, thereby promoting cancer initiation and progression through cancer- and immune-related pathways. Methods: We extracted DNA from 402 fresh frozen tissues from 289 women in the NCI-Maryland Breast Cancer Cohort, including 185 tumor samples, 113 additional paired adjacent normal samples, and 104 normal tissues from reduction mammoplasty. Census-tract level socioeconomic deprivation was measured via a Neighborhood Deprivation Index (NDI) using the geocoded addresses from our study participants. DNA methylation values were acquired using the Illumina Infinium MethylationEPIC 850K Beadchip. We conducted a differentially methylated probe (DMP) analysis between tumor and adjacent normal tissue to characterize methylation profiles by NDI status. We also used methylCIBERSORT to estimate immune cell subpopulation differences by tissue type and NDI status. Results: NDI was significantly associated with self-reported race in our cohort in both normal (p<0.0001, 95% CI -4.32, -2.58) and tumor (p<0.0001, 95% CI -4.22, -2.79) tissue. Our DMP analysis showed more significant methylation events (hypo- or hyper- methylation of the tumor tissue compared to adjacent normal tissue) in the NDI high group compared to the NDI low group. We also identified five CpG sites that were significantly hypomethylated in the tumors of the NDI high group, including two tumor suppressor genes, LRIG1 (p=1.99 x10-10) and WWOX (p=6.47 x 10-9). These methylation changes translated to an inverse relationship between gene expression for these tumor suppressor genes and NDI. We also identified significantly lower neutrophils in the NDI high tumors compared to NDI low tumors (p=0.001, 95% CI -0.112, -0.028). Conclusions: Overall, our analysis provides evidence that high neighborhood deprivation can lead to pro-tumorigenic changes in DNA methylation and gene expression that may impact the immune microenvironment, breast cancer progression, and overall survival.
2023-10-15 | GSE225845 | GEO
Project description:Background: Low socioeconomic status (SES) has been linked to chronic stress and poorer health outcomes for marginalized communities in the U.S. The biological processes mediating the impact of SES on health to promote chronic diseases, such as cancer, remain poorly understood. Here, we aim to determine how changes in DNA methylation are linked to neighborhood-level socioeconomic deprivation, thereby promoting cancer initiation and progression through cancer- and immune-related pathways. Methods: We extracted DNA from 402 fresh frozen tissues from 289 women in the NCI-Maryland Breast Cancer Cohort, including 185 tumor samples, 113 additional paired adjacent normal samples, and 104 normal tissues from reduction mammoplasty. Census-tract level socioeconomic deprivation was measured via a Neighborhood Deprivation Index (NDI) using the geocoded addresses from our study participants. DNA methylation values were acquired using the Illumina Infinium MethylationEPIC 850K Beadchip. We conducted a differentially methylated probe (DMP) analysis between tumor and adjacent normal tissue to characterize methylation profiles by NDI status. We also used methylCIBERSORT to estimate immune cell subpopulation differences by tissue type and NDI status. Results: NDI was significantly associated with self-reported race in our cohort in both normal (p<0.0001, 95% CI -4.32, -2.58) and tumor (p<0.0001, 95% CI -4.22, -2.79) tissue. Our DMP analysis showed more significant methylation events (hypo- or hyper- methylation of the tumor tissue compared to adjacent normal tissue) in the NDI high group compared to the NDI low group. We also identified five CpG sites that were significantly hypomethylated in the tumors of the NDI high group, including two tumor suppressor genes, LRIG1 (p=1.99 x10-10) and WWOX (p=6.47 x 10-9). These methylation changes translated to an inverse relationship between gene expression for these tumor suppressor genes and NDI. We also identified significantly lower neutrophils in the NDI high tumors compared to NDI low tumors (p=0.001, 95% CI -0.112, -0.028). Conclusions: Overall, our analysis provides evidence that high neighborhood deprivation can lead to pro-tumorigenic changes in DNA methylation and gene expression that may impact the immune microenvironment, breast cancer progression, and overall survival.
2023-10-13 | GSE225846 | GEO
Project description:High neighborhood deprivation impacts DNA methylation and gene expression in cancer-related genes
| PRJNA937706 | ENA
Project description:High neighborhood deprivation impacts DNA methylation and gene expression in cancer-related genes (MethylationEPIC)
| PRJNA937710 | ENA
Project description:High neighborhood deprivation impacts DNA methylation and gene expression in cancer-related genes (RNA-Seq)
| PRJNA937709 | ENA
Project description:Children show stronger cooperative behavior in experimental settings as they get older, but little is known about how the environment of a child shapes this development. In adults, prosocial behavior toward strangers is markedly decreased in low socio-economic status (SES) neighborhoods, suggesting that environmental harshness has a negative impact on some prosocial behaviors. Similar results have been obtained with 9-year-olds recruited from low vs. high SES schools. In the current study, we investigate whether these findings generalize to a younger age group and a developing country. Specifically, we worked with a sample of thirty-nine 6- to 7-year-olds in two neighborhoods in a single city in Romania. Using a "Quality Dictator Game" that offers greater resolution than previous measures, we find that children living in the harsher neighborhood behave less prosocially toward a stranger than children living in the less harsh neighborhood.
| S-EPMC5107739 | biostudies-literature
Project description:Sleep is critical for normal brain function and mental health. However, the molecular mechanisms mediating the impact of sleep loss on both cognition and the sleep electroencephalogram remain mostly unknown. Acute sleep loss impacts brain gene expression broadly. These data contributed to current hypotheses regarding the role for sleep in metabolism, synaptic plasticity and neuroprotection. These changes in gene expression likely underlie increased sleep intensity following sleep deprivation (SD). Here we tested the hypothesis that epigenetic mechanisms coordinate the gene expression response driven by SD. We found that SD altered the cortical genome-wide distribution of two major epigenetic marks: DNA methylation and hydroxymethylation. DNA methylation differences were enriched in gene pathways involved in neuritogenesis and synaptic plasticity, whereas large changes (>4000 sites) in hydroxymethylation where observed in genes linked to cytoskeleton, signaling and neurotransmission, which closely matches SD-dependent changes in the transcriptome. Moreover, this epigenetic remodeling applied to elements previously linked to sleep need (for example, Arc and Egr1) and synaptic partners of Neuroligin-1 (Nlgn1; for example, Dlg4, Nrxn1 and Nlgn3), which we recently identified as a regulator of sleep intensity following SD. We show here that Nlgn1 mutant mice display an enhanced slow-wave slope during non-rapid eye movement sleep following SD but this mutation does not affect SD-dependent changes in gene expression, suggesting that the Nlgn pathway acts downstream to mechanisms triggering gene expression changes in SD. These data reveal that acute SD reprograms the epigenetic landscape, providing a unique molecular route by which sleep can impact brain function and health.
| S-EPMC3905230 | biostudies-literature
Project description:Researchers hypothesized that telomere shortening facilitates carcinogenesis. Previous studies found inconsistent associations between blood leukocyte telomere length (LTL) and cancer. Epigenetic reprogramming of telomere maintenance mechanisms may help explain this inconsistency. We examined associations between DNA methylation in telomere-related genes (TRG) and cancer. We analyzed 475 participants providing 889 samples 1 to 3 times (median follow-up, 10.1 years) from 1999 to 2013 in the Normative Aging Study. All participants were cancer-free at each visit and blood leukocytes profiled using the Illumina 450K array. Of 121 participants who developed cancer, 34 had prostate cancer, 10 melanoma, 34 unknown skin malignancies, and 43 another cancer. We examined 2,651 CpGs from 80 TRGs and applied a combination of Cox and mixed models to identify CpGs prospectively associated with cancer (at FDR < 0.05). We also explored trajectories of DNA methylation, logistic regression stratified by time to diagnosis/censoring, and cross-sectional models of LTL at first blood draw. We identified 30 CpGs on 23 TRGs whose methylation was positively associated with cancer incidence (β = 1.0-6.93) and one protective CpG in MAD1L1 (β = -0.65), of which 87% were located in TRG promoters. Methylation trajectories of 21 CpGs increased in cancer cases relative to controls; at 4 to 8 years prediagnosis/censoring, 17 CpGs were positively associated with cancer. Three CpGs were cross-sectionally associated with LTL. TRG methylation may be a mechanism through which LTL dynamics reflect cancer risk. Future research should confirm these findings and explore potential mechanisms underlying these findings, including telomere maintenance and DNA repair dysfunction. Cancer Prev Res; 11(8); 511-22. ©2018 AACR.
| S-EPMC6800137 | biostudies-literature
Project description:BackgroundDespite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation.ResultsA total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03-3.19).ConclusionsIncreased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival.
| S-EPMC11301857 | biostudies-literature
Project description:Drug overdoses are a national and global epidemic. However, while overdoses are inextricably linked to social, demographic, and geographical determinants, geospatial patterns of drug-related admissions and overdoses at the neighborhood level remain poorly studied. The objective of this paper is to investigate spatial distributions of patients admitted for drug-related admissions and overdoses from a large, urban, tertiary care center using electronic health record data. Additionally, these spatial distributions were adjusted for a validated socioeconomic index called the Area Deprivation Index (ADI). We showed spatial heterogeneity in patients admitted for opioid, amphetamine, and psychostimulant-related diagnoses and overdoses. While ADI was associated with drug-related admissions, it did not correct for spatial variations and could not account alone for this spatial heterogeneity.
| S-EPMC7704893 | biostudies-literature