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. 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. 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.

中文翻译：

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头颈癌幸存者的表观遗传分层揭示了番茄红素水平、饮酒量和免疫调节基因甲基化的差异。

炎症与头颈癌 (HNC) 的较高复发率和死亡率有关。虽然使患者易患炎症状态加剧的生物学机制在很大程度上仍不为人知，但已提出 DNA 甲基化可以反映全身性炎症。在此分析中，我们试图通过根据白细胞中的 DNA 甲基化谱对个体进行分层来识别 HNC 幸存者中有意义的表观遗传模式。我们使用层次聚类来揭示 HNC 幸存者中三种不同的甲基化模式。每组都在炎症通路（包括细胞因子和 B 细胞受体信号传导）中显示出独特的甲基化特征。此外，我们检查了与炎症相关的生理、临床和生活方式参数，例如循环类胡萝卜素和细胞因子水平、癌症治疗类型、和饮酒。具体而言，我们确定了一组幸存者，他们的转录和翻译调节因子以及 T 细胞受体信号通路中的基因具有显着差异甲基化，包括 CD40 配体 (CD40LG) 和 Tec 蛋白酪氨酸激酶 (TEC) 的高甲基化以及CD8A。该组还显示出高循环番茄红素水平。我们确定了另一个在 toll 样受体 (TLR) 信号通路中具有独特甲基化的组，包括 TLR5 的低甲基化，TLR5 是核因子-kappa B 激酶复合物 (CHUK) 抑制剂的一个组成部分，以及两种丝裂原活化蛋白激酶 ( MAP3K8 和 MAP2K3）。该组还具有线粒体核糖体基因的高甲基化以及较高的饮酒率。番茄红素之间的相关性，