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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.
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Acknowledgements
The authors are grateful for the long-term support of the families who come to their lab multiple times in the course of the longitudinal study of the third generation offspring that made this research possible.
Financial & competing interests disclosure
Funding for this study was provided by NIAAA grants AA018289, AA005909, AA008082, AA015168 and AA021746 to SY Hill. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The University of Pittsburgh Institutional Review Board approved this protocol.