Dataset Information

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

ABSTRACT: BACKGROUND:Estrogen receptor-? (ER-?) is a transcriptional regulator, which mediates estrogen-dependent breast development, as well as breast tumorigenesis. The influence of epigenetic regulation of ER-? 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-? 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-? 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-? methylation at B2, and cellular heterogeneity, we observed an inverse association between B4 average ER-? 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-? 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-? methylation relative to the lowest. The association between ER-? 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-? may modulate adolescent response to estrogen and breast composition, which may influence breast cancer risk in adulthood.

SUBMITTER: Binder AM

PROVIDER: S-EPMC6172836 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

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

Binder Alexandra M AM Stiemsma Leah T LT Keller Kristen K van Otterdijk Sanne D SD Mericq Verónica V Pereira Ana A Santos José L JL Shepherd John J Michels Karin B KB

Clinical epigenetics 20181004 1

<h4>Background</h4>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 t ...[more]

PMID: 30286806

Similar Datasets

Project description:BackgroundEpidemiologic evidence suggests that environmental factors acting as endocrine disrupting chemicals (EDCs) are associated with mammographic breast density and the risk of breast cancer. Exposure to EDCs during puberty, a period of rapid breast development, may affect susceptibility to breast carcinogenesis.MethodsIn a cohort of 366 Chilean adolescents from the Growth and Obesity Cohort Study, we evaluated the relation between urinary concentrations of 15 suspected EDC biomarkers across three pubertal time points (Tanner breast stage 1 (B1), 4 (B4), and 1-year post-menarche) and breast fibroglandular volume (FGV; percent FGV [%FGV] and absolute FGV [aFGV]) and total breast volume (tBV) at 2-years post-menarche. We used linear mixed models to test differences in creatinine-corrected EDC biomarker concentrations at B4 and 1-year post-menarche compared to B1 and calculated intraclass correlation coefficients (ICC) of EDC concentrations across time points to appraise the consistency of measurements. We fit multivariable generalized estimating equations (GEEs) to evaluate windows of susceptibility for the association between log10-transformed EDCs and log10-transformed breast outcomes. GEEs were adjusted for age, body fat percentage, total caloric intake, and maternal education.ResultsUrinary EDC biomarker concentrations highly varied across pubertal time points (ICC range 0.01-0.30). For 12 EDCs, biomarker concentrations decreased over time. Triclosan measured at 1-year post-menarche was inversely associated with %FGV at 2-years post-menarche (β = -0.025, 95 % confidence interval = -0.041, -0.008). Mono(2-ethyl-5-carboxypentyl) phthalate and the sum of di(2-ethylhexyl) phthalate metabolite concentrations at B4 were positively associated with aFGV and tBV at 2-years post-menarche. No measured phenols were associated with aFGV and tBV, while no measured parabens were associated with %FGV and aFGV.ConclusionsOur study suggests relatively high variability in EDC biomarker concentrations across the peripubertal time period. We also found evidence to suggest that there may be pubertal windows of susceptibility to select EDCs for the association with adolescent breast density.

Project description:BackgroundAdolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects. Currently, health care providers have varying practices without evidence-based standards, thus investigating potential differences between oral and transdermal preparations is essential. The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen (OCEE), oral 17β estradiol (OBE), or transdermal 17β estradiol (TBE) on biochemical profiles and feminization in girls with ovarian failure.Study design20 prepubertal adolescent females with ovarian failure, ages 12-18 years, were randomized to OCEE (n = 8), OBE (n = 7), or TBE (n = 5) for 24 months. Estrogen replacement was initiated at a low dose (0.15 mg OCEE, 0.25 mg OBE, or 0.0125 mg TBE) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE, 1 mg/d OBE, or 0.05 mg/d TBE. At 18 months, micronized progesterone was added to induce menstrual cycles. Biochemical markers including sex hormones, inflammatory markers, liver enzymes, coagulation factors, and lipids were obtained at baseline and 6 month intervals. Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance (ANOVA). The effect of progesterone on biochemical markers was evaluated with the paired t-test.ResultsMean (±SE) estradiol levels at maximum estrogen dose (18 months) were higher in the TBE group (53 ± 19 pg/mL) compared to OCEE (14 ± 5 pg/mL) and OBE (12 ± 5 pg/mL) (p ≤ 0.01). The TBE and OBE groups had more effective feminization (100% Tanner 3 breast stage at 18 months). There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone.ConclusionsTreatment with transdermal 17β estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients. OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls, but larger prospective randomized trials are required.Trial registrationClinical trials identifierNCT01023178.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets