In utero exposure to diethylstilbestrol and blood DNA methylation in women ages 40-59 years from the sister study

PLoS One. 2015 Mar 9;10(3):e0118757. doi: 10.1371/journal.pone.0118757. eCollection 2015.

Abstract

In utero exposure to diethylstilbestrol (DES) has been associated with increased risk of adverse health outcomes such as fertility problems and vaginal as well as breast cancer. Animal studies have linked prenatal DES exposure to lasting DNA methylation changes. We investigated genome-wide DNA methylation and in utero DES exposure in a sample of non-Hispanic white women aged 40-59 years from the Sister Study, a large United States cohort study of women with a family history of breast cancer. Using questionnaire information from women and their mothers, we selected 100 women whose mothers reported taking DES while pregnant and 100 control women whose mothers had not taken DES. DNA methylation in blood was measured at 485,577 CpG sites using the Illumina HumanMethylation450 BeadChip. Associations between CpG methylation and DES exposure status were analyzed using robust linear regression with adjustment for blood cell composition and multiple comparisons. Although four CpGs had p<105, after accounting for multiple comparisons using the false discovery rate (FDR), none reached genome-wide significance. In conclusion, adult women exposed to DES in utero had no evidence of large persistent changes in blood DNA methylation.

Publication types

  • Clinical Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cohort Studies
  • CpG Islands
  • DNA / blood*
  • DNA / drug effects
  • DNA Methylation*
  • Diethylstilbestrol / adverse effects*
  • Estrogens, Non-Steroidal / adverse effects*
  • Female
  • Humans
  • Linear Models
  • Middle Aged
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / genetics
  • Siblings
  • Surveys and Questionnaires

Substances

  • Estrogens, Non-Steroidal
  • Diethylstilbestrol
  • DNA

Grant support

This study was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.