Abstract:
BACKGROUND:Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. RESULTS:Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). CONCLUSIONS:Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Hofstatter EW,Horvath S,Dalela D,Gupta P,Chagpar AB,Wali VB,Bossuyt V,Storniolo AM,Hatzis C,Patwardhan G,Von Wahlde MK,Butler M,Epstein L,Stavris K,Sturrock T,Au A,Kwei S,Pusztai Ldoi
10.1186/s13148-018-0534-8subject
Has Abstractpub_date
2018-08-29 00:00:00pages
112issue
1eissn
1868-7075issn
1868-7083pii
10.1186/s13148-018-0534-8journal_volume
10pub_type
杂志文章,多中心研究abstract:BACKGROUND:Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next-generation sequencing in representative...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0195-4
更新日期:2016-03-15 00:00:00
abstract::Researchers have begun to examine epigenetic alterations in the placenta, making key advances in understanding the epigenetic regulatory mechanisms of the placenta that define underlying processes of human development and disease. Examining changes in microRNA (miRNA) expression associated with environmental exposures...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0046-2
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). Subjects with FASD show significant neurological deficits, ranging from microencephaly, neurobehavioral, and mental heal...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0416-5
更新日期:2017-10-23 00:00:00
abstract:INTRODUCTION:DNA methylation of CpG islands within the promoter region of genes is an epigenetic modification with an important role in the development of cancer and it is typically mediated by DNA methyltransferases (DNMTs). In cancer cells, global hypomethylation of the genome as a whole and regional hypermethylation...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-7
更新日期:2013-05-02 00:00:00
abstract:BACKGROUND:Pancreatic cancer has a 5-year survival rate of only 5-7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagn...
journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
doi:10.1186/s13148-016-0286-2
更新日期:2016-11-16 00:00:00
abstract::Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction p...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-010-0018-y
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Hypericin-mediated photodynamic therapy (HY-PDT) has recently captured increased attention as an alternative minimally invasive anticancer treatment, although cancer cells may acquire resistance. Therefore, combination treatments may be necessary to enhance HY-PDT efficacy. Histone deacetylase inhibitors (HD...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0359-x
更新日期:2017-06-08 00:00:00
abstract:Background:This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. Methods:A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0432-5
更新日期:2017-12-20 00:00:00
abstract:BACKGROUND:Splicing is more efficient when coupled with transcription and it has been proposed that nucleosomes enriched in exons are important for splice site recognition. Lynch syndrome is a familial cancer syndrome that can be caused by the autosomal dominant inheritance of splice site mutations in the MutL homolog ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-014-0032-6
更新日期:2014-12-13 00:00:00
abstract:BACKGROUNDS:Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizz...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00875-9
更新日期:2020-06-09 00:00:00
abstract:: Lower than normal levels of oxygen (hypoxia) is a hallmark of all solid tumours rendering them frequently resistant to both radiotherapy and chemotherapy regimes. Furthermore, tumour hypoxia and activation of the hypoxia inducible factor (HIF) transcriptional pathway is associated with poorer prognosis. Driven by bot...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-3-9
更新日期:2011-12-05 00:00:00
abstract:BACKGROUND:The tumor-specific microregional effects of the anticancer agent RRx-001, a novel epigenetic-based radio/chemosensitizer with nitrogen oxide-donating properties in phase II clinical trials, were investigated with whole tissue section quantitative immunohistological staining in mouse SCCVII and human U87 tumo...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0220-7
更新日期:2016-05-11 00:00:00
abstract::In this letter to the editor, we highlight some concerns with a recently published method to estimate gestational age at delivery from DNA methylation data. We conduct novel analyses to highlight the implications of different choices in study design and statistical methods for the prediction of phenotypes from methyla...
journal_title:Clinical epigenetics
pub_type: 信件
doi:10.1186/s13148-017-0402-y
更新日期:2017-09-15 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus type 1 (HIV-1) latency represents the major barrier to virus eradication in infected individuals because cells harboring latent HIV-1 provirus are not affected by current antiretroviral therapy (ART). We previously demonstrated that DNA methylation of HIV-1 long terminal repeat (...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0185-6
更新日期:2016-02-19 00:00:00
abstract:BACKGROUND:Chronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00903-8
更新日期:2020-07-27 00:00:00
abstract:BACKGROUND:Aging is a complex phenomenon and characterized by a progressive decline in physiology and function of adult tissues. However, it hasn't been well established of the correlation between aging and global DNA methylation and hydroxymethylation that regulate the growth and development of higher organisms. RESU...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0109-x
更新日期:2015-07-23 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) screening can effectively reduce disease-related mortality by detecting CRC at earlier stages. We have previously demonstrated that the presence of SDC2 methylation in stool DNA is significantly associated with the occurrence of CRC regardless of clinical stage. The aim of this study ...
journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
doi:10.1186/s13148-019-0642-0
更新日期:2019-03-15 00:00:00
abstract:BACKGROUND:In vitro follicle culture (IFC), as applied in the mouse system, allows the growth and maturation of a large number of immature preantral follicles to become mature and competent oocytes. In the human oncofertility clinic, there is increasing interest in developing this technique as an alternative to ovarian...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0794-y
更新日期:2019-12-19 00:00:00
abstract::Remodeling of the sperm epigenome by lifestyle factors before conception could account for altered metabolism in the next generation offspring. Here, we hypothesized that endurance training changes the epigenome of human spermatozoa. Using small RNA (sRNA) sequencing and reduced representation bisulfite sequencing (RR...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0446-7
更新日期:2018-01-25 00:00:00
abstract::The study of DNA methylation in development and disease has 'exploded' as a field in recent years, with three major classes of measurement now routine. These encompass (i) locus-specific, (ii) genome-scale/wide and (iii) 'global' methylation approaches. Measures of global methylation refer to the level of 5-methylcyto...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0311-0
更新日期:2017-01-13 00:00:00
abstract:BACKGROUND:The DNA modification 5-hydroxymethylcytosine (5hmC) is now referred to as the sixth base of DNA with evidence of tissue-specific patterns and correlation with gene regulation and expression. This epigenetic mark was recently reported as a potential biomarker for multiple types of cancer, but its application ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0368-9
更新日期:2017-07-14 00:00:00
abstract:BACKGROUND:The transcription factor Snail2 is a repressor of E-cadherin expression during carcinogenesis; however, the specific mechanisms involved in this process in human colorectal cancer (CRC) remain largely unknown. METHOD:We checked the expression of Snail2 in several clinical CRC specimens. Then, we established...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0592-y
更新日期:2018-12-12 00:00:00
abstract:BACKGROUND:The autoimmune disease systemic lupus erythematosus (SLE) has a modified epigenome with modified tri-methylation of histone H3 lysine 4 (H3K4me3) at specific loci across the genome. H3K4me3 is a canonical chromatin mark of active transcription. Recent studies have suggested that H3K4me3 breadth has an import...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0179-4
更新日期:2016-02-02 00:00:00
abstract:BACKGROUND:Modification of DNA by methylation of cytosines at CpG dinucleotides is a widespread phenomenon that leads to changes in gene expression, thereby influencing and regulating many biological processes. Recent technical advances in the genome-wide determination of single-base DNA-methylation enabled epigenome-w...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-014-0040-6
更新日期:2015-01-22 00:00:00
abstract::Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychos...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0038-2
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Emerging evidence has shown that MUC1 and TFF2 play crucial roles in the H. pylori-infected pathogenesis of gastric cancer (GC). A recent study revealed that H. pylori infection induced obviously increased Tff2 methylation levels in Muc1-/- mice compared with controls. However, little is known of the molecul...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00832-6
更新日期:2020-03-02 00:00:00
abstract:BACKGROUND:Apabetalone (RVX-208) is a bromodomain and extraterminal protein inhibitor (BETi) that in phase II trials reduced the relative risk (RR) of major adverse cardiac events (MACE) in patients with cardiovascular disease (CVD) by 44% and in diabetic CVD patients by 57% on top of statins. A phase III trial, BETonM...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0696-z
更新日期:2019-07-12 00:00:00
abstract::Lymphocytes from the peripheral blood of patients with prostate cancer-the most frequent (noncutaneous) tumor in men-display epigenetic aberrations (altered modes of allelic replication) characteristic of the malignant phenotype. The present study aims to determine whether replication aberrations add certainty to the ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0029-3
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Both forms of facioscapulohumeral muscular dystrophy (FSHD) are associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite. Chromatin changes due to large deletions of heterochromatin (FSHD1) or mutations in chromatin regulatory proteins (FSHD2) lead to relaxation of epigenetic...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0072-6
更新日期:2015-03-29 00:00:00
abstract:BACKGROUND:About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We theref...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0161-6
更新日期:2015-12-12 00:00:00