Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption,
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RESEARCH
Open Access
Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption, and methylation of immune regulatory genes Laura Moody1, Sylvia L. Crowder2, Andrew D. Fruge3, Julie L. Locher4, Wendy Demark-Wahnefried5, Laura Q. Rogers5, Ashley Delk-Licata5, William R. Carroll6, Sharon A. Spencer7, Molly Black2, John W. Erdman Jr1,2, Hong Chen1,2, Yuan-Xiang Pan1,2,8 and Anna E. Arthur1,2,9*
Abstract Background: Inflammation has been associated with higher rates of recurrence and mortality in head and neck cancer (HNC). While the biological mechanisms predisposing patients to heightened inflammatory states remain largely unknown, DNA methylation has been proposed to reflect systemic inflammation. In this analysis, we attempt to identify meaningful epigenetic patterns in HNC survivors by stratifying individuals based on DNA methylation profiles in leukocytes. Results: We used hierarchical clustering to uncover three distinct methylation patterns among HNC survivors. Each group displayed a unique methylation signature in inflammatory pathways including cytokine and B-cell receptor signaling. Additionally, we examined physiological, clinical, and lifestyle parameters related to inflammation, such as circulating carotenoid and cytokine levels, cancer treatment type, and alcohol consumption. Specifically, we identified one group of survivors who had significant differential methylation of transcriptional and translational regulators as well as genes in the T-cell receptor signaling pathway, including hypermethylation of CD40 ligand (CD40LG) and Tec protein tyrosine kinase (TEC) and hypomethylation of CD8A. This group also displayed high circulating lycopene levels. We identified another group that had distinctive methylation in the toll-like receptor (TLR) signaling pathway, including hypomethylation of TLR5, a component of the inhibitor of nuclear factor-kappa B kinase complex (CHUK), and two mitogen-activated protein kinases (MAP3K8 and MAP2K3). This group also had hypermethylation of mitochondrial ribosomal genes along with higher rates of alcohol consumption. Conclusion: The correlation between lycopene, alcohol consumption, DNA methylation, and inflammation warrants further investigation and may have implications in future recommendations and interventions to impact health outcomes in HNC survivors. Keywords: Head and neck cancer, Survivors, DNA methylation, Inflammation, Lycopene, Alcohol * Correspondence: [email protected] 1 Division of Nutritional Sciences, University of Illinois at Urbana–Champaign, Urbana, IL 61801, USA 2 Department of Food Science and Human Nutrition, University of Illinois at Urbana–Champaign, 386A Bevier Hall, MC-182, 905 South Goodwin Avenue, Urbana, IL 61801, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction
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