| Title |
FOXA1 hypermethylation: link between parity and ER-negative breast cancer in African American women?
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, July 2017
|
| DOI | 10.1007/s10549-017-4418-y |
| Pubmed ID | |
| Authors |
Allyson C. Espinal, Matthew F. Buas, Dan Wang, David Ting-Yuan Cheng, Lara Sucheston-Campbell, Qiang Hu, Li Yan, Rochelle Payne-Ondracek, Eduardo Cortes, Li Tang, Zhihong Gong, Gary Zirpoli, Thaer Khoury, Song Yao, Angela Omilian, Kitaw Demissie, Elisa V. Bandera, Song Liu, Christine B. Ambrosone, Michael J. Higgins |
| Abstract |
Reproductive factors, particularly parity, have differential effects on breast cancer risk according to estrogen receptor (ER) status, especially among African American (AA) women. One mechanism could be through DNA methylation, leading to altered expression levels of genes important in cell fate decisions. Using the Illumina 450K BeadChip, we compared DNA methylation levels in paraffin-archived tumor samples from 383 AA and 350 European American (EA) women in the Women's Circle of Health Study (WCHS). We combined 450K profiles with RNA-seq data and prioritized genes based on differential methylation by race, correlation between methylation and gene expression, and biological function. We measured tumor protein expression and assessed its relationship to DNA methylation. We evaluated associations between reproductive characteristics and DNA methylation using linear regression. 410 loci were differentially methylated by race, with the majority unique to ER- tumors. FOXA1 was hypermethylated in tumors from AA versus EA women with ER- cancer, and increased DNA methylation correlated with reduced RNA and protein expression. Importantly, parity was positively associated with FOXA1 methylation among AA women with ER- tumors (P = 0.022), as was number of births (P = 0.026), particularly among those who did not breastfeed (P = 0.008). These same relationships were not observed among EA women, although statistical power was more limited. Methylation and expression of FOXA1 is likely impacted by parity and breastfeeding. Because FOXA1 regulates a luminal gene expression signature in progenitor cells and represses the basal phenotype, this could be a mechanism that links these reproductive exposures with ER- breast cancer. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 19% |
| Student > Master | 5 | 14% |
| Student > Bachelor | 3 | 8% |
| Student > Postgraduate | 3 | 8% |
| Professor | 3 | 8% |
| Other | 6 | 16% |
| Unknown | 10 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 22% |
| Nursing and Health Professions | 7 | 19% |
| Biochemistry, Genetics and Molecular Biology | 5 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Agricultural and Biological Sciences | 1 | 3% |
| Other | 3 | 8% |
| Unknown | 12 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 June 2018.
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#20,483,282
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Outputs from Breast Cancer Research and Treatment
#4,130
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#276,337
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Outputs of similar age from Breast Cancer Research and Treatment
#71
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