Methylation of progesterone receptor isoform A promoter in normal breast tissue: An epigenetic link between early age at menarche and risk of breast cancer?

Daraei, Abdolreza and Izadi, Pantea and Khorasani, Ghasemali and Nafissi, Nahid and Naghizadeh, Mohammad Mehdi and Younosi, Nasim and Meysamie, Alipasha and Mansoori, Yaser and Nariman-Saleh-Fam, Ziba and Bastami, Milad and Saadatian, Zahra and Zendehbad, Zahra and Tavakkoly-Bazzaz, Javad (2019) Methylation of progesterone receptor isoform A promoter in normal breast tissue: An epigenetic link between early age at menarche and risk of breast cancer? JOURNAL OF CELLULAR BIOCHEMISTRY, 120 (8). pp. 12393-12401.

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Abstract

Emerging evidence indicates that some altered patterns of methylation that occur in breast tumors may also be found in breast tissue of healthy women in relation to the breast cancer (BC) risk factors. Progesterone receptor (PR) isoform alpha is a crucial regulator of breast hormone responsiveness and its hypermethylation plays an important role in the initiation and development of breast tumors. However, such a methylation change in healthy women and its link with the different risk factors has not yet been investigated. In the present study, we aimed to examine the relationship of possible methylation changes within a critical region in the promoter CpG island of PGR-alpha (progesterone receptor alpha) gene in the healthy women with a set of reproductive and nonreproductive BC risk factors. The breast tissues were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. The genomic DNA was extracted from the breast tissues and the methylation level of PGR-alpha promoter CpG island was determined by using MeDIP-qPCR assay. Using regression analysis, we found that increasing menarche age is inversely associated with the high methylation of PGR-alpha promoter (beta = -0.790, SE = 0.362; P = 0.031). Although lactating women had more methylation than nonlactating women (P = 0.026, the t test), this result was not confirmed by regression models. Such an observation may be helpful in better understanding of the underlying mechanisms by which early age at menarche increases the risk of BC. However, this perspective requires further validations in larger studies of more subjects as well as the inclusion of other related genes.

Item Type: Article
Uncontrolled Keywords: age at menarche; normal breast tissue; PGR-alpha promoter CpG island methylation changes; reproductive BC risk factors
Subjects: QV Pharmacology
Depositing User: Unnamed user with email eprints@fums.ac.ir
Date Deposited: 04 Jan 2020 09:24
Last Modified: 04 Jan 2020 09:24
URI: http://eprints.fums.ac.ir/id/eprint/2585

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