Inverse association between estrogen receptor-α DNA methylation and breast composition in adolescent Chilean girls

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dc.contributor.authorBinder, Alexandra M.
dc.contributor.authorSantos Martín, José Luis
dc.contributor.authorStiemsma, Leah T.
dc.contributor.authorKeller, Kristen.
dc.contributor.authorvan Otterdijk, Sanne D.
dc.contributor.authorMericq, Verónica.
dc.contributor.authorPereira, Ana.
dc.contributor.authorShepherd, John.
dc.contributor.authorMichels, Karin B.
dc.date.accessioned2019-10-17T14:23:03Z
dc.date.available2019-10-17T14:23:03Z
dc.date.issued2018
dc.date.updated2019-10-14T18:26:03Z
dc.description.abstractAbstract Background Estrogen receptor-α (ER-α) is a transcriptional regulator, which mediates estrogen-dependent breast development, as well as breast tumorigenesis. The influence of epigenetic regulation of ER-α on adolescent breast composition has not been previously studied and could serve as a marker of pubertal health and susceptibility to breast cancer. We investigated the association between ER-α DNA methylation in leukocytes and breast composition in adolescent Chilean girls enrolled in the Growth and Obesity Cohort Study (GOCS) in Santiago, Chile. Breast composition (total breast volume (BV; cm3), fibroglandular volume (FGV; cm3), and percent fibroglandular volume (%FGV)) was measured at breast Tanner stage 4 (B4). ER-α promoter DNA methylation was assessed by pyrosequencing in blood samples collected at breast Tanner stages 2 (B2; n = 256) and B4 (n = 338). Results After adjusting for fat percentage at breast density measurement, ER-α methylation at B2, and cellular heterogeneity, we observed an inverse association between B4 average ER-α DNA methylation and BV and FGV. Geometric mean BV was 15% lower (95% CI: − 28%, − 1%) among girls in the highest quartile of B4 ER-α methylation (6.96–23.60%) relative to the lowest (0.78–3.37%). Similarly, FGV was 19% lower (95% CI: − 33%, − 2%) among girls in the highest quartile of B4 ER-α methylation relative to the lowest. The association between ER-α methylation and breast composition was not significantly modified by body fat percentage and was not influenced by pubertal timing. Conclusions These findings suggest that the methylation profile of ER-α may modulate adolescent response to estrogen and breast composition, which may influence breast cancer risk in adulthood.
dc.fuente.origenBiomed Central
dc.identifier.citationClinical Epigenetics. 2018 Oct 04;10(1):122
dc.identifier.doi10.1186/s13148-018-0553-5
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26692
dc.identifier.wosidWOS:000446408200001
dc.issue.numeroNo. 122
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final12
dc.pagina.inicio1
dc.revistaClinical Epigeneticses_ES
dc.rightsacceso abierto
dc.rights.holderThe Author(s).
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.subject.otherMamaes_ES
dc.subject.otherMamas Neoplasmases_ES
dc.subject.otherEstrógenoses_ES
dc.subject.otherMetabolismoes_ES
dc.titleInverse association between estrogen receptor-α DNA methylation and breast composition in adolescent Chilean girlses_ES
dc.typeartículo
dc.volumenVol. 10
sipa.codpersvinculados1005923
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