Obesity and menopause modify the epigenomic profile of breast cancer.
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Authors
Crujeiras, Ana BDiaz-Lagares, Angel
Stefansson, Olafur A
Macias-Gonzalez, Manuel
Sandoval, Juan
Cueva, Juan
Lopez-Lopez, Rafael
Moran, Sebastian
Jonasson, Jon G
Tryggvadottir, Laufey
Olafsdottir, Elinborg
Tinahones, Francisco J
Carreira, Marcos C
Casanueva, Felipe F
Esteller, Manel
Issue Date
2017
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Obesity and menopause modify the epigenomic profile of breast cancer. 2017, 24 (7):351-363 Endocr. Relat. CancerAbstract
Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern. Intriguingly, the DNA methylation pattern identified in association with the high-risk group (postmenopausal women with high BMI (>25) and premenopausal women with normal or low BMI < 25) exclusively characterized by hypermethylation of 1287 CpG sites as compared with the low-risk group. These CpG sites included the promoter region of fourteen protein-coding genes of which CpG methylation over the ZNF577 promoter region represents the top scoring associated event. In an independent cohort, the ZNF577 promoter methylation remained statistically significant in association with the high-risk group. Additionally, the impact of ZNF577 promoter methylation on mRNA expression levels was demonstrated in breast cancer cell lines after treatment with a demethylating agent (5-azacytidine). In conclusion, the epigenome of breast tumors is affected by a complex interaction between BMI and menopausal status. The ZNF577 methylation quantification is clearly relevant for the development of novel biomarkers of precision therapy in breast cancer.Description
To access publisher's full text version of this article click on the hyperlink belowAdditional Links
http://erc.endocrinology-journals.org/content/early/2017/04/25/ERC-16-0565.full.pdfRights
Archived with thanks to Endocrine-related cancerae974a485f413a2113503eed53cd6c53
10.1530/ERC-16-0565
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