FOXA1 hypermethylation: link between parity and ER-negative breast cancer in African American women?
- 29.07.2017
- Epidemiology
Erschienen in:
- Verfasst von
- 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
- Erschienen in
- Breast Cancer Research and Treatment | Ausgabe 2/2017
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Anzeige
- Titel
- FOXA1 hypermethylation: link between parity and ER-negative breast cancer in African American women?
- Verfasst von
-
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
- Publikationsdatum
- 29.07.2017
- Verlag
- Springer US
- Erschienen in
-
Breast Cancer Research and Treatment / Ausgabe 2/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217 - DOI
- https://doi.org/10.1007/s10549-017-4418-y
Dieser Inhalt ist nur sichtbar, wenn du eingeloggt bist und die entsprechende Berechtigung hast.
Dieser Inhalt ist nur sichtbar, wenn du eingeloggt bist und die entsprechende Berechtigung hast.
