An Epigenome-Wide Analysis of Socioeconomic Position and Tumor DNA Methylation in Breast Cancer Patients
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PROVIDER: PRJNA940716 | ENA |
REPOSITORIES: ENA
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Project description:Background: Disadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP. Methods: Based on tumor DNA methylation data from the Illumina 450K array from 694 breast cancer patients in the Women’s Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases. Results: We identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in -adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women, and did not differ by tumor estrogen receptor (ER) status. Conclusions: In a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the -adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues which might be relevant to cancer development and progression.
2023-03-31 | GSE226569 | GEO
Project description:BackgroundDisadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP.MethodsBased on tumor DNA methylation data from the Illumina 450 K array from 694 breast cancer patients in the Women's Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases.ResultsWe identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in β-adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women and did not differ by tumor estrogen receptor (ER) status.ConclusionsIn a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the β-adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues, which might be relevant to cancer development and progression.
| S-EPMC10131486 | biostudies-literature
Project description:Acute colon cancer surgery has a poor 90-day mortality of 21.0% compared with only 3% after elective colorectal cancer surgery in Denmark. The high mortality after acute colon cancer surgery compared with elective surgery emphasizes the importance of identifying factors associated with acute onset and poor short-term survival after acute surgery. Socioeconomic position has previously showed to be a risk factor for acute versus elective onset of colorectal cancer. Furthermore, if patients with low socioeconomic position have higher postoperative mortality this could reflect differences in the treatment of patients according to their socioeconomic position.
The aim of the clinical study is:
1. To examine if patients with short education, low income, living alone, or living in rural areas are more likely to undergo acute colorectal cancer surgery than elective surgery compared with patients with longer educations, higher income, living with a partner, or living in urban areas.
2. To examine if there is an association between education, income, cohabitation, or urbanicity and 1-year mortality after acute colorectal cancer surgery.
| 2277284 | ecrin-mdr-crc
Project description:Background: Disparities in socioeconomic status have been associated with adverse pregnancy outcomes, including preterm birth and fetal growth restriction. As the barrier between maternal exposures and the fetus, the placenta has been proposed to play a role in the mechanisms leading to poor health outcomes seen with socioeconomic disadvantage. We hypothesized that exposure to lower SES during pregnancy may lead to altered placental DNA methylation (DNAme) that is in turn associated with other pregnancy outcomes. Methods: Placental samples from the Stress, Pregnancy, and Health Study (SPAH) study (n=493) were processed for DNAme analysis using the Illumina Infinium MethylationEPIC BeadChip array. Linear modelling was used to assess whether placental DNAme was associated with Socioeconomic Position, Financial Resources, and/or Disadvantage. Results: At FDR <0.05 and |∆β| >0.05, we observed only 2 CpGs associated with Socioeconomic Position after correcting for gestational age and ancestry, while at a less stringent |∆β| >0.02 threshold there were 77 and 22 CpG associations with Socioeconomic Position and Disadvantage respectively. However, these changes seemed to be explained by genetic variation influencing DNAme in combination with population stratification by socioeconomic status. We did observe associations between socioeconomic status and DNAme-inferred cell composition and epigenetic age acceleration, with intrinsic (p=0.047) and extrinsic (p=0.050) age acceleration being slightly accelerated with lower levels of Socioeconomic Position. Financial Resources and Disadvantage SES trended in the same direction as Social Position, with lower socioeconomic status seen with higher levels of age acceleration, though not reaching significance. No meaningful associations in sex stratified analyses were identified, although XX placentas showed higher cytotrophoblast:syncytiotrophoblast ratio than XY placentas (p=0.00013). Conclusions: Our results emphasize the importance in placental studies involving diverse cohorts to account for genetic variation in order to avoid false findings. This study also demonstrates the challenges with elucidating mechanisms underlying socioeconomic associated outcomes, given the complex nature of correlated variables. Further investigation is required to elucidate whether epigenetic age acceleration is an adverse effect of exposure to prenatal maternal stress associated with socioeconomic disparities, or alternatively, if placental epigenetic aging is a potential healthy adaption to pregnancy complications that increase the risk of preterm delivery.
2026-02-10 | GSE307289 | GEO
Project description:BackgroundSocioeconomic experiences are recognized determinants of health, and recent work has shown that social disadvantages in early life may induce sustained biological changes at molecular level that are detectable later in life. However, the dynamics and persistence of biological embedding of socioeconomic position (SEP) remains vastly unexplored.MethodsUsing the data from the ALSPAC birth cohort, we performed epigenome-wide association studies of DNA methylation changes at three life stages (birth, n = 914; childhood at mean age 7.5 years, n = 973; and adolescence at mean age 15.5 years, n = 974), measured using the Illumina HumanMethylation450 Beadchip, in relation to pregnancy SEP indicators (maternal and paternal education and occupation).ResultsAcross the four early life SEP metrics investigated, only maternal education was associated with methylation levels at birth, and four CpGs mapped to SULF1, GLB1L2 and RPUSD1 genes were identified [false discovery rate (FDR)-corrected P-value <0.05]. No epigenetic signature was found associated with maternal education in child samples, but methylation levels at 20 CpG loci were found significantly associated with maternal education in adolescence. Although no overlap was found between the differentially methylated CpG sites at different ages, we identified two CpG sites at birth and during adolescence which are 219 bp apart in the SULF1 gene that encodes an heparan sulphatase involved in modulation of signalling pathways. Using data from an independent birth cohort, the ENVIRONAGE cohort, we were not able to replicate these findings.ConclusionsTaken together, our results suggest that parental SEP, and particularly maternal education, may influence the offspring's methylome at birth and adolescence.
| S-EPMC6443021 | biostudies-literature
Project description:This study evaluated the hypothesis that prenatal maternal socioeconomic status (SES) adversity is associated with DNA methylation in the placenta. SES adversity was defined by the presence of, as well as a summative count of, four factors: less than college education, single marital status, food and nutritional service assistance, and public health insurance. Epigenome-wide DNA methylation was assessed using the Illumina EPIC array in 426 placentas from a sample of infants born < 28 weeks of gestation from the Extremely Low Gestational Age Newborn cohort. Associations between SES adversity and DNA methylation were assessed with robust linear regressions adjusted for covariates and controlled the false discovery rate at < 10%. We also examined whether such associations were sex specific. Indicators of SES adversity were associated with differential methylation at 33 CpG sites. Of the 33 identified CpG sites, 19 (57.6%) displayed increased methylation, and 14 (42.4%) displayed decreased methylation in association with at least one of the SES adversity factors. Sex differences were observed in DNA methylation associated with summative SES score; in which placentas derived from female pregnancies showed more robust differential CpG methylation than placentas from male pregnancies. Maternal SES adversity was associated with differential methylation of genes with key role in gene transcription and placental function, potentially altering immunity and stress response. Further investigation is needed to evaluate the role of epigenetic differences in mediating the association between maternal socioeconomic status during pregnancy and later life health outcomes in children.
| S-EPMC6615526 | biostudies-literature
Project description:Epigenome-wide DNA methylation analysis in inflammatory breast cancer
| PRJNA997959 | ENA
Project description:BackgroundDNA methylation is a potential biomarker for early detection of breast cancer. However, robust evidence of a prospective relationship between DNA methylation patterns and breast cancer risk is still lacking. The objective of this study is to provide a systematic analysis of the findings of epigenome-wide DNA methylation studies on breast cancer risk, in light of their methodological strengths and weaknesses.MethodsWe searched major databases (MEDLINE, EMBASE, Web of Science, CENTRAL) from inception up to 30th June 2019, for observational or intervention studies investigating the association between epigenome-wide DNA methylation (using the HM450k or EPIC BeadChip), measured in any type of human sample, and breast cancer risk. A pre-established protocol was drawn up following the Cochrane Reviews rigorous methodology. Study selection, data abstraction, and risk of bias assessment were performed by at least two investigators. A qualitative synthesis and systematic comparison of the strengths and weaknesses of studies was performed.ResultsOverall, 20 studies using the HM450k BeadChip were included, 17 of which had measured blood-derived DNA methylation. There was a consistent trend toward an association of global blood-derived DNA hypomethylation and higher epigenetic age with higher risk of breast cancer. The strength of associations was modest for global hypomethylation and relatively weak for most of epigenetic age algorithms. Differences in length of follow-up periods may have influenced the ability to detect associations, as studies reporting follow-up periods shorter than 10 years were more likely to observe an association with global DNA methylation. Probe-wise differential methylation analyses identified between one and 806 differentially methylated CpGs positions in 10 studies. None of the identified differentially methylated sites overlapped between studies. Three studies used breast tissue DNA and suffered major methodological issues that precludes any conclusion. Overall risk of bias was critical mainly because of incomplete control of confounding. Important issues relative to data preprocessing could have limited the consistency of results.ConclusionsGlobal DNA methylation may be a short-term predictor of breast cancer risk. Further studies with rigorous methodology are needed to determine spatial distribution of DNA hypomethylation and identify differentially methylated sites associated with risk of breast cancer.Prospero registration numberCRD42020147244.
| S-EPMC7603741 | biostudies-literature
Project description:In the early 2000s, emerging SARS-CoV-2, which is highly pathogenic, posed a great threat to public health. During COVID-19, epigenetic regulation is deemed to be an important part of the pathophysiology and illness severity. Using the Illumina Infinium Methylation EPIC BeadChip (850 K), we investigated genome-wide differences in DNA methylation between healthy subjects and COVID-19 patients with different disease severities. We conducted a combined analysis and selected 35 "marker" genes that could indicate a SARS-CoV-2 infection, including 12 (ATHL1, CHN2, CHST15, CPLX2, CRHR2, DCAKD, GNAI2, HECW1, HYAL1, MIR510, PDE11A, and SMG6) situated in the promoter region. The functions and pathways of differentially methylated genes were enriched in biological processes, signal transduction, and the immune system. In the "Severe versus Mild" group, differentially methylated genes, after eliminating duplicates, were used for PPI analyses. The four hub genes (GNG7, GNAS, PRKCZ, and PRKAG2) that had the highest degree of nodes were identified and among them, GNG7 and GNAS genes expressions were also downregulated in the severe group in sequencing results. Above all, the results suggest that GNG7 and GNAS may play a non-ignorable role in the progression of COVID-19. In conclusion, the identified key genes and related pathways in the current study can be used to study the molecular mechanisms of COVID-19 and may provide possibilities for specific treatments.
| S-EPMC8441705 | biostudies-literature
Project description:Differential DNA methylation is a potential marker of breast cancer risk. Few studies have investigated DNA methylation changes in normal breast tissue and were largely confounded by cancer field effects. To detect methylation changes in normal breast epithelium that are causally associated with breast cancer occurrence, we used a nested case-control study design based on a prospective cohort of patients diagnosed with a primary invasive hormone receptor-positive breast cancer. Twenty patients diagnosed with a contralateral breast cancer (CBC) were matched (1:1) with 20 patients who did not develop a CBC on relevant risk factors. Differentially methylated Cytosine-phosphate-Guanines (CpGs) and regions in normal breast epithelium were identified using an epigenome-wide DNA methylation assay and robust linear regressions. Analyses were replicated in two independent sets of normal breast tissue and blood. We identified 7315 CpGs (FDR < 0.05), 52 passing strict Bonferroni correction (p < 1.22 × 10-7) and 43 mapping to known genes involved in metabolic diseases with significant enrichment (p < 0.01) of pathways involving fatty acids metabolic processes. Four differentially methylated genes were detected in both site-specific and regions analyses (LHX2, TFAP2B, JAKMIP1, SEPT9), and three genes overlapped all three datasets (POM121L2, KCNQ1, CLEC4C). Once validated, the seven differentially methylated genes distinguishing women who developed and who did not develop a sporadic breast cancer could be used to enhance breast cancer risk-stratification, and allow implementation of targeted screening and preventive strategies that would ultimately improve breast cancer prognosis.
| S-EPMC7690691 | biostudies-literature