Document Detail


Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression, and cancer.
MedLine Citation:
PMID:  24287154     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Epigenetic marks are extensively altered in cancer, but may also change in normal tissues with age, which is the primary risk factor for most cancers. We conducted an epigenome-wide study to identify age-related methylation sites and examine their relationship to cancer and other underlying epigenetic marks. We analyzed 1,006 blood DNA samples of women aged 35 to 76 from the Sister Study, and found that 7,694 (28%) of the 27,578 CpGs assayed were associated with age (false discovery rate, FDR q < 0.05). Using independent datasets we confirmed 749 (")high-confidence(") age-related CpG (arCpGs) sites in normal blood. Based on The Cancer Genome Atlas (TCGA) data we show that these age-related changes are largely concordant in a broad variety of normal tissues, and that a significantly higher (71 to 91%, p< 10(-74)) than expected proportion of increasingly-methylated arCpGs (IM-arCpGs) were over-methylated in a wide variety of tumor types. IM-arCpGs sites occurred almost exclusively at CpG islands and were disproportionately marked with the repressive H3K27me3 histone modification (p< 1x10(-50)). Genes containing these IM-arCpG sites were highly enriched for developmental and signaling pathways (p< 10(-10)). Our findings suggest that as cells acquire methylation at age-related sites they have a lower threshold for malignant transformation that may explain in part, the increase in cancer incidence with age.
Authors:
Zongli Xu; Jack A Taylor
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-28
Journal Detail:
Title:  Carcinogenesis     Volume:  -     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC.
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