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Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters

The idea that susceptibility to breast cancer is determined not only through inherited germline mutations but also by epigenetic changes induced by alterations in hormonal environment during fetal development is gaining increasing support. Using findings obtained in human and animal studies, this re...

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Autor principal: Hilakivi-Clarke, Leena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053091/
https://www.ncbi.nlm.nih.gov/pubmed/25032259
http://dx.doi.org/10.1186/bcr3649
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author Hilakivi-Clarke, Leena
author_facet Hilakivi-Clarke, Leena
author_sort Hilakivi-Clarke, Leena
collection PubMed
description The idea that susceptibility to breast cancer is determined not only through inherited germline mutations but also by epigenetic changes induced by alterations in hormonal environment during fetal development is gaining increasing support. Using findings obtained in human and animal studies, this review addresses the mechanisms that may explain why daughters of mothers who took synthetic estrogen diethylstilbestrol (DES) during pregnancy have two times higher breast cancer risk than women who were not exposed to it. The mechanisms likely involve epigenetic alterations, such as increased DNA methylation and modifications in histones and microRNA expression. Further, these alterations may target genes that regulate stem cells and prevent differentiation of their daughter cells. Recent findings in a preclinical model suggest that not only are women exposed to DES in utero at an increased risk of developing breast cancer, but this risk may extend to their daughters and granddaughters as well. It is critical, therefore, to determine if the increased risk is driven by epigenetic alterations in genes that increase susceptibility to breast cancer and if these alterations are reversible.
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spelling pubmed-40530912014-10-30 Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters Hilakivi-Clarke, Leena Breast Cancer Res Review The idea that susceptibility to breast cancer is determined not only through inherited germline mutations but also by epigenetic changes induced by alterations in hormonal environment during fetal development is gaining increasing support. Using findings obtained in human and animal studies, this review addresses the mechanisms that may explain why daughters of mothers who took synthetic estrogen diethylstilbestrol (DES) during pregnancy have two times higher breast cancer risk than women who were not exposed to it. The mechanisms likely involve epigenetic alterations, such as increased DNA methylation and modifications in histones and microRNA expression. Further, these alterations may target genes that regulate stem cells and prevent differentiation of their daughter cells. Recent findings in a preclinical model suggest that not only are women exposed to DES in utero at an increased risk of developing breast cancer, but this risk may extend to their daughters and granddaughters as well. It is critical, therefore, to determine if the increased risk is driven by epigenetic alterations in genes that increase susceptibility to breast cancer and if these alterations are reversible. BioMed Central 2014 2014-04-30 /pmc/articles/PMC4053091/ /pubmed/25032259 http://dx.doi.org/10.1186/bcr3649 Text en Copyright © 2014 Hilakivi-Clarke; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 The licensee has exclusive rights to distribute this article, in any medium, for 6 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Hilakivi-Clarke, Leena
Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters
title Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters
title_full Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters
title_fullStr Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters
title_full_unstemmed Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters
title_short Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters
title_sort maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053091/
https://www.ncbi.nlm.nih.gov/pubmed/25032259
http://dx.doi.org/10.1186/bcr3649
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