Mediation analysis of alcohol consumption, DNA methylation, and epithelial ovarian cancer

Dongyan Wu, Haitao Yang, Stacey J. Winham, Yanina Natanzon, Devin C. Koestler, Tiane Luo, Brooke L. Fridley, Ellen L. Goode, Yanbo Zhang, Yuehua Cui

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Epigenetic factors and consumption of alcohol, which suppresses DNA methylation, may influence the development and progression of epithelial ovarian cancer (EOC). However, there is a lack of understanding whether these factors interact to affect the EOC risk. In this study, we aimed to gain insight into this relationship by identifying leukocyte-derived DNA methylation markers acting as potential mediators of alcohol-associated EOC. We implemented a causal inference test (CIT) and the VanderWeele and Vansteelandt multiple mediator model to examine CpG sites that mediate the association between alcohol consumption and EOC risk. We modified one step of the CIT by adopting a high-dimensional inference procedure. The data were based on 196 cases and 202 age-matched controls from the Mayo Clinic Ovarian Cancer Case-Control Study. Implementation of the CIT test revealed two CpG sites (cg09358725, cg11016563), which represent potential mediators of the relationship between alcohol consumption and EOC case-control status. Implementation of the VanderWeele and Vansteelandt multiple mediator model further revealed that these two CpGs were the key mediators. Decreased methylation at both CpGs was more common in cases who drank alcohol at the time of enrollment vs. those who did not. cg11016563 resides in TRPC6 which has been previously shown to be overexpressed in EOC. These findings suggest two CpGs may serve as novel biomarkers for EOC susceptibility.

Original languageEnglish (US)
Pages (from-to)339-348
Number of pages10
JournalJournal of Human Genetics
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2018

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    Wu, D., Yang, H., Winham, S. J., Natanzon, Y., Koestler, D. C., Luo, T., Fridley, B. L., Goode, E. L., Zhang, Y., & Cui, Y. (2018). Mediation analysis of alcohol consumption, DNA methylation, and epithelial ovarian cancer. Journal of Human Genetics, 63(3), 339-348. https://doi.org/10.1038/s10038-017-0385-8