Browsing by Author "Shin, Dong M."

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    Association of Epigenetic Age Acceleration With Risk Factors, Survival, and Quality of Life in Patients With Head and Neck Cancer
    (Elsevier, 2021) Xiao, Canhua; Miller, Andrew H.; Peng, Gang; Levine, Morgan E.; Conneely, Karen N.; Zhao, Hongyu; Eldridge, Ronald C.; Wommack, Evanthia C.; Jeon, Sangchoon; Higgins, Kristin A.; Shin, Dong M.; Saba, Nabil F.; Smith, Alicia K.; Burtness, Barbara; Park, Henry S.; Irwin, Melinda L.; Ferrucci, Leah M.; Ulrich, Bryan; Qian, David C.; Beitler, Jonathan J.; Bruner, Deborah W.; Medical and Molecular Genetics, School of Medicine
    Purpose: Epigenetic age acceleration (EAA) is robustly linked with mortality and morbidity. This study examined risk factors of EAA and its association with overall survival (OS), progression-free survival (PFS), and quality of life (QOL) in patients with head and neck cancer (HNC) receiving radiation therapy. Methods and materials: Patients without distant metastasis were enrolled and followed before and at the end of radiation therapy and at 6 and 12 months after radiation therapy. EAA was calculated with DNAmPhenoAge at all 4 time points. Risk factors included demographic characteristics, lifestyle, clinical characteristics, treatment-related symptoms, and blood biomarkers. Survival data were collected until August 2020, and QOL was measured using Functional Assessment of Cancer Therapy-HNC. Results: Increased comorbidity, symptoms unrelated to human papilloma virus, and more severe treatment-related symptoms were associated with higher EAA (P = .03 to P < .001). A nonlinear association (quadratic) between body mass index (BMI) and EAA was observed: decreased BMI (<35 kg/m2; P = .04) and increased BMI (≥35 kg/m2; P = .01) were linked to higher EAA. Increased EAA (per year) was associated with worse OS (hazard ratio [HR], 1.11 [95% confidence interval {CI}, 1.03-1.18; P = .004]; HR, 1.10 [95% CI, 1.01-1.19; P = .02] for EAA at 6 and 12 months after treatment, respectively) and PFS (HR, 1.10 [95% CI, 1.02-1.19; P = .02]; HR, 1.14 [95% CI, 1.06-1.23; P < .001]; and HR, 1.08 [95% CI, 1.02-1.14; P = .01]) for EAA before, immediately after, and 6 months after radiation therapy, respectively) and QOL over time (β = -0.61; P = .001). An average of 3.25 to 3.33 years of age acceleration across time, which was responsible for 33% to 44% higher HRs of OS and PFS, was observed in those who died or developed recurrence compared with those who did not (all P < .001). Conclusions: Compared with demographic and lifestyle factors, clinical characteristics were more likely to contribute to faster biological aging in patients with HNC. Acceleration in epigenetic age resulted in more aggressive adverse events, including OS and PFS. EAA could be considered as a marker for cancer outcomes, and decelerating aging could improve survival and QOL.
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    The role of the gut microbiome in cancer-related fatigue: pilot study on epigenetic mechanisms
    (Springer, 2021) Xiao, Canhua; Fedirko, Veronika; Beitler, Jonathan; Bai, Jinbing; Peng, Gang; Zhou, Chao; Gu, Jianlei; Zhao, Hongyu; Lin, I-Hsin; Chico, Cynthia E.; Jeon, Sangchoon; Knobf, Tish M.; Conneely, Karen N.; Higgins, Kristin; Shin, Dong M.; Saba, Nabil; Miller, Andrew; Bruner, Deborah; Medical and Molecular Genetics, School of Medicine
    Purpose: Recent evidence supports a key role of gut microbiome in brain health. We conducted a pilot study to assess associations of gut microbiome with cancer-related fatigue and explore the associations with DNA methylation changes. Methods: Self-reported Multidimensional Fatigue Inventory and stool samples were collected at pre-radiotherapy and one-month post-radiotherapy in patients with head and neck cancer. Gut microbiome data were obtained by sequencing the 16S ribosomal ribonucleic acid gene. DNA methylation changes in the blood were assessed using Illumina Methylation EPIC BeadChip. Results: We observed significantly different gut microbiota patterns among patients with high vs. low fatigue across time. This pattern was characterized by low relative abundance in short-chain fatty acid-producing taxa (family Ruminococcaceae, genera Subdoligranulum and Faecalibacterium; all p < 0.05), with high abundance in taxa associated with inflammation (genera Family XIII AD3011 and Erysipelatoclostridium; all p < 0.05) for high-fatigue group. We identified nine KEGG Orthology pathways significantly different between high- vs. low-fatigue groups over time (all p < 0.001), including pathways related to fatty acid synthesis and oxidation, inflammation, and brain function. Gene set enrichment analysis (GSEA) was performed on the top differentially methylated CpG sites that were associated with the taxa and fatigue. All biological processes from the GSEA were related to immune responses and inflammation (FDR < 0.05). Conclusions: Our results suggest different patterns of the gut microbiota in cancer patients with high vs. low fatigue. Results from functional pathways and DNA methylation analyses indicate that inflammation is likely to be the major driver in the gut-brain axis for cancer-related fatigue.