{"doi":"10.1002/cncr.33641","title":"Epigenetic age acceleration, fatigue, and inflammation in patients undergoing radiation therapy for head and neck cancer: A longitudinal study","abstract":"BACKGROUND: The authors measured epigenetic age acceleration (EAA) during and after cancer treatment and its association with inflammation and fatigue, which is a debilitating symptom in patients with cancer. METHODS: Patients who had head and neck cancer without distant metastases were assessed before, immediately after, and at 6 months and 12 months postradiotherapy. Blood DNA methylation was assessed using a proprietary bead chip (the Illumina MethylationEPIC BeadChip). EAA was calculated using the Levine epigenetic clock (DNAmPhenoAge), adjusted for chronological age. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. Inflammatory markers were measured using standard techniques. RESULTS: Most patients (N = 133) were men, White, had advanced disease, and received concurrent chemoradiation. EAA changes over time were significant, with the largest increase (4.9 years) observed immediately after radiotherapy (P < .001). Increased EAA was associated with elevated fatigue (P = .003) over time, and patients who had severe fatigue experienced 3.1 years higher EAA than those who had low fatigue (P < .001), which was more prominent (5.6 years; P = .018) for patients who had human papillomavirus-unrelated disease at 12 months posttreatment. EAA was also positively associated with inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), over time (P < .001), and patients who had high CRP and IL-6 levels exhibited increases of 4.6 and 5.9 years, respectively, in EAA compared with those who had low CRP and IL-6 levels (P < .001). CRP and IL-6 mediated the association between EAA and fatigue (CRP: 95% CI, 0.060-0.279; IL-6: 95% CI, 0.024-0.220). CONCLUSIONS: Patients with head and neck cancer experienced increased EAA, especially immediately after treatment completion. EAA was associated with greater fatigue and inflammation, including 1 year after treatment. Inflammation may be a target to reduce the impact of age acceleration on poor functional outcomes.","journal":"Cancer","year":2021,"id":153890,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":66,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":326592,"name":"Jonathan J. Beitler","orcid":"0000-0002-1519-2071","position":1,"is_corresponding":false},{"id":326594,"name":"Gang Peng","orcid":"0000-0003-0307-9351","position":2,"is_corresponding":false},{"id":218505,"name":"Morgan E. Levine","orcid":"0000-0001-9890-9324","position":3,"is_corresponding":false},{"id":326599,"name":"Karen N. Conneely","orcid":"0000-0002-1994-6934","position":4,"is_corresponding":false},{"id":652275,"name":"Hongyu Zhao","orcid":"0000-0002-9968-5737","position":5,"is_corresponding":false},{"id":320521,"name":"Jennifer C. Felger","orcid":"0000-0003-4354-2267","position":6,"is_corresponding":false},{"id":652869,"name":"Evanthia C. Wommack","orcid":null,"position":7,"is_corresponding":false},{"id":327763,"name":"Cynthia E. Chico","orcid":null,"position":8,"is_corresponding":false},{"id":277227,"name":"Sangchoon Jeon","orcid":"0000-0003-2855-2053","position":9,"is_corresponding":false},{"id":267372,"name":"Kristin Higgins","orcid":"0000-0003-1496-9878","position":10,"is_corresponding":false},{"id":69848,"name":"Dong M. Shin","orcid":"0000-0002-8245-4174","position":11,"is_corresponding":false},{"id":241868,"name":"Nabil F. Saba","orcid":"0000-0003-4972-1477","position":12,"is_corresponding":false},{"id":103785,"name":"Barbara Burtness","orcid":"0000-0003-4660-1859","position":13,"is_corresponding":false},{"id":326601,"name":"Deborah Watkins Bruner","orcid":"0000-0002-5770-9948","position":14,"is_corresponding":false},{"id":326600,"name":"Andrew H. Miller","orcid":"0000-0001-8260-7997","position":15,"is_corresponding":false},{"id":326590,"name":"Canhua Xiao","orcid":"0000-0003-1391-5325","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:43:44.759273Z","pmid":"34027995","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}