Cross-generational effects of alcohol dependence in humans on HRAS and TP53 methylation in offspring

Epigenomics. 2017 Sep;9(9):1189-1203. doi: 10.2217/epi-2017-0052. Epub 2017 Aug 11.

Abstract

Aim: We hypothesized that cross-generational effects of alcohol exposure could alter DNA methylation and expression of the HRAS oncogene and TP53 tumor suppressor gene that drive cancer development.

Methods: DNA methylation of the HRAS and TP53 genes was tested in samples from young participants (Mean age of 13.4 years).

Results: Controlling for both personal use and maternal use of substances during pregnancy, familial alcohol dependence was associated with hypomethylation of CpG sites in the HRAS promoter region and hypermethylation of the TP53 gene.

Conclusion: The results suggest that ancestral exposure to alcohol can have enduring effects that impact epigenetic processes such as DNA methylation that controls expression of genes that drive cancer development such as HRAS and TP53.

Keywords: HRAS; TP53; alcohol dependence.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Alcoholism / genetics*
  • Case-Control Studies
  • Child
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)