PMID- 28708432
OWN - NLM
STAT- MEDLINE
DCOM- 20170921
LR  - 20210816
IS  - 1945-0257 (Electronic)
IS  - 1945-0257 (Linking)
VI  - 21
IP  - 8
DP  - 2017 Aug
TI  - Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing 
      Link with Breast Cancer Risk Factors?
PG  - 464-470
LID - 10.1089/gtmb.2017.0028 [doi]
AB  - BACKGROUND: Reproductive history and obesity are among the well-recognized risk 
      factors in the development of breast cancer, which are partially mediated by the 
      increased exposure of breast tissues to estrogens. However, only a few studies 
      have investigated the link between these risk factors and the pattern of 
      methylation signatures in the breast tissue of healthy women. The role of the 
      estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the 
      development of breast cancer. Thus, it is speculated that such ESR1 epigenetic 
      changes may be influenced or shaped by obesity and reproductive history-related 
      factors before and during breast carcinogenesis. MATERIALS AND METHODS: Breast 
      samples were collected from 120 cancer-free women who had undergone cosmetic 
      mammoplasty. DNA was extracted from the breast tissues and, then, the methylation 
      levels at the promoter and exon 1 regions of the ESR1 gene CpG island were 
      determined by using the methylated DNA immunoprecipitation-quantitative PCR 
      assay. RESULTS: The methylation level of the ESR1 promoter observed in women with 
      a body mass index (BMI) >/=30 kg/m(2) (p </= 0.001) was higher than in the subgroups 
      of women of BMI <25 kg/m(2) (p < 0.001) and BMI 25-29 kg/m(2) (p < 0.001) and was 
      also higher in postmenopausal women compared with that in premenopausal women 
      (p = 0.046). Pearson correlation coefficient analyses also showed that the high 
      methylation of the ESR1 promoter was correlated with increasing age (r = -0.246, 
      p = 0.007) and BMI (r = -0.331, p </= 0.001). Finally, linear multivariate 
      regression revealed a significant association between high methylation rates in 
      the ESR1 gene promoter and increased BMI (beta = -0.285, 95% CI = -0.457 to -0.113, 
      p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was 
      found in the BMI >/= 30 kg/m(2) subgroup compared to the BMI 25-29 kg/m(2) subgroup 
      (p = 0.023). CONCLUSION: These findings provide new hints about the relationship 
      between epigenetic changes within the ESR1 gene CpG island and postmenopausal 
      obesity and aging in cancer-free women. In terms of lifestyle intervention 
      opportunities, this study also highlights the significance and feasibility of 
      such interventions for BMI as a modifiable risk factor.
FAU - Daraei, Abdolreza
AU  - Daraei A
AD  - 1 Department of Medical Genetics, School of Medicine, Tehran University of 
      Medical Sciences , Tehran, Iran .
FAU - Izadi, Pantea
AU  - Izadi P
AD  - 1 Department of Medical Genetics, School of Medicine, Tehran University of 
      Medical Sciences , Tehran, Iran .
FAU - Khorasani, Ghasemali
AU  - Khorasani G
AD  - 2 Division of Plastic and Reconstructive Surgery, Imam Khomeini Hospital Complex, 
      Tehran University of Medical Sciences , Tehran, Iran .
FAU - Nafissi, Nahid
AU  - Nafissi N
AD  - 3 Surgical Department, School of Medicine, Iran University of Medical Sciences , 
      Tehran, Iran .
FAU - Naghizadeh, Mohammad Mehdi
AU  - Naghizadeh MM
AD  - 4 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences , 
      Fasa, Iran .
FAU - Younosi, Nasim
AU  - Younosi N
AD  - 5 Surgical Department, School of Medicine, Shahid Beheshti University of Medical 
      Sciences , Tehran, Iran .
FAU - Meysamie, Alipasha
AU  - Meysamie A
AD  - 6 Community and Preventive Medicine Department, Medical Faculty, Tehran 
      University of Medical Sciences , Tehran, Iran .
FAU - Mansoori, Yaser
AU  - Mansoori Y
AD  - 4 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences , 
      Fasa, Iran .
FAU - Bastami, Milad
AU  - Bastami M
AD  - 7 Department of Medical Genetics, Faculty of Medicine, Tabriz University of 
      Medical Sciences , Tabriz, Iran .
FAU - Tavakkoly-Bazzaz, Javad
AU  - Tavakkoly-Bazzaz J
AD  - 1 Department of Medical Genetics, School of Medicine, Tehran University of 
      Medical Sciences , Tehran, Iran .
LA  - eng
PT  - Journal Article
DEP - 20170714
PL  - United States
TA  - Genet Test Mol Biomarkers
JT  - Genetic testing and molecular biomarkers
JID - 101494210
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/genetics
MH  - Body Mass Index
MH  - Breast Neoplasms/genetics
MH  - CpG Islands/genetics
MH  - DNA Methylation/genetics
MH  - Epigenesis, Genetic/*genetics
MH  - Epigenomics/methods
MH  - Estrogen Receptor alpha/*genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - Genetic Testing
MH  - Humans
MH  - Middle Aged
MH  - Obesity
MH  - Promoter Regions, Genetic/genetics
MH  - Risk Factors
OTO - NOTNLM
OT  - CpG island methylation
OT  - ESR1 gene
OT  - MeDIP assay
OT  - breast cancer risk factors
OT  - normal breast tissue
EDAT- 2017/07/15 06:00
MHDA- 2017/09/22 06:00
CRDT- 2017/07/15 06:00
PHST- 2017/07/15 06:00 [pubmed]
PHST- 2017/09/22 06:00 [medline]
PHST- 2017/07/15 06:00 [entrez]
AID - 10.1089/gtmb.2017.0028 [doi]
PST - ppublish
SO  - Genet Test Mol Biomarkers. 2017 Aug;21(8):464-470. doi: 10.1089/gtmb.2017.0028. 
      Epub 2017 Jul 14.