Endogenous sex hormone exposure and repetitive element DNA methylation in healthy postmenopausal women.
Cancer Causes Control
; 28(12): 1369-1379, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28929436
ABSTRACT
PURPOSE:
Epigenetic mechanisms may help to explain the complex and heterogeneous relation between sex hormones and cancer. Few studies have investigated the effects of sex hormones on epigenetic markers related to cancer risk such as levels of methylation within repetitive DNA elements. Our objective was to describe the association between endogenous sex hormone exposure and levels of LINE-1 and Alu methylation in healthy postmenopausal women.METHODS:
We nested a cross-sectional study within the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2006). Study participants consisted of healthy postmenopausal women who had never been diagnosed with cancer (n = 289). Sex hormone exposures included serum concentrations of estradiol, estrone, testosterone, androstenedione, and sex hormone-binding globulin. We estimated the participants' lifetime number of menstrual cycles (LNMC) as a proxy for cumulative exposure to ovarian sex hormones. Buffy coat samples were assessed for DNA methylation. Linear regression was used to model the associations of interest and to control for confounding.RESULTS:
Both estradiol and estrone had a significant positive dose-response association with LINE-1 methylation. LNMC was associated with both LINE-1 and Alu methylation. Specifically, LNMC had a non-linear "U-shaped" association with LINE-1 methylation regardless of folate intake and a negative linear association with Alu methylation, but only amongst low folate consumers. Androgen exposure was not associated with either outcome.CONCLUSION:
Current and cumulative estrogen exposure was associated with repetitive element DNA methylation in a group of healthy postmenopausal women. LINE-1 and Alu methylation may be epigenetic mechanisms through which estrogen exposure impacts cancer risk.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônios Esteroides Gonadais
/
Globulina de Ligação a Hormônio Sexual
/
Pós-Menopausa
/
Metilação de DNA
/
Elementos Nucleotídeos Longos e Dispersos
/
Elementos Alu
/
Estrogênios
/
Androgênios
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Cancer Causes Control
Assunto da revista:
EPIDEMIOLOGIA
/
NEOPLASIAS
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá