当前位置： SCI文献检索 > BREAST CANCER RESEARCH期刊下所有文献 > Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

Abstract：

BACKGROUND:The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. METHODS:Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. RESULTS:We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value <0.01) with subject age. Notably, DNA methylation was not strongly associated with the other evaluated breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). CONCLUSIONS:DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Johnson KC,Houseman EA,King JE,Christensen BC

doi

10.1186/s13058-017-0873-y

subject

Has Abstract

pub_date

2017-07-10 00:00:00

pages

issue

eissn

1465-5411

issn

1465-542X

pii

10.1186/s13058-017-0873-y

journal_volume

pub_type

杂志文章

在线工具

Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.