{"doi":"10.1093/jnci/djae046","title":"Health-related quality of life and DNA methylation-based aging biomarkers among survivors of childhood cancer","abstract":"BACKGROUND: Childhood cancer survivors are at high risk for morbidity and mortality and poor patient-reported outcomes, typically health-related quality of life (HRQOL). However, associations between DNA methylation-based aging biomarkers and HRQOL have not been evaluated. METHODS: DNA methylation was generated with Infinium EPIC BeadChip on blood-derived DNA (median for age at blood draw = 34.5 years, range = 18.5-66.6 years), and HRQOL was assessed with age at survey (mean = 32.3 years, range = 18.4-64.5 years) from 2206 survivors in the St Jude Lifetime Cohort. DNA methylation-based aging biomarkers, including epigenetic age using multiple clocks (eg, GrimAge) and others (eg, DNAmB2M: beta-2-microglobulin; DNAmADM: adrenomedullin), were derived from the DNAm Age Calculator (https://dnamage.genetics.ucla.edu). HRQOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey to capture 8 domains and physical and mental component summaries. General linear models evaluated associations between HRQOL and epigenetic age acceleration (EAA; eg, EAA_GrimAge) or other age-adjusted DNA methylation-based biomarkers (eg, ageadj_DNAmB2M) after adjusting for age at blood draw, sex, cancer treatments, and DNA methylation-based surrogate for smoking pack-years. All P values were 2-sided. RESULTS: Worse HRQOL was associated with greater EAA_GrimAge (physical component summaries: β = -0.18 years, 95% confidence interval [CI] = -0.251 to -0.11 years; P = 1.85 × 10-5; and 4 individual HRQOL domains), followed by ageadj_DNAmB2M (physical component summaries: β = -0.08 years, 95% CI = -0.124 to -0.037 years; P = .003; and 3 individual HRQOL domains) and ageadj_DNAmADM (physical component summaries: β = -0.082 years, 95% CI = -0.125 to -0.039 years; P = .002; and 2 HRQOL domains). EAA_Hannum (Hannum clock) was not associated with any HRQOL. CONCLUSIONS: Overall and domain-specific measures of HRQOL are associated with DNA methylation measures of biological aging. Future longitudinal studies should test biological aging as a potential mechanism underlying the association between poor HRQOL and increased risk of clinically assessed adverse health outcomes.","journal":"JNCI Journal of the National Cancer Institute","year":2024,"id":478502,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6976,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337395,"name":"Yue Pan","orcid":"0000-0001-5015-9691","position":1,"is_corresponding":false},{"id":955679,"name":"Cheng Chen","orcid":"0000-0001-9773-2993","position":2,"is_corresponding":false},{"id":887271,"name":"Qian Dong","orcid":"0000-0002-2028-9046","position":3,"is_corresponding":false},{"id":295314,"name":"Xijun Zhang","orcid":"0009-0002-8434-5673","position":4,"is_corresponding":false},{"id":309087,"name":"Nan Song","orcid":"0000-0002-9182-1060","position":5,"is_corresponding":false},{"id":255624,"name":"Kyla Shelton","orcid":"0000-0002-0135-0745","position":6,"is_corresponding":false},{"id":5544,"name":"John Easton","orcid":"0000-0003-4503-6608","position":7,"is_corresponding":false},{"id":252145,"name":"Heather L. Mulder","orcid":"0000-0003-2024-9498","position":8,"is_corresponding":false},{"id":1812,"name":"Jinghui Zhang","orcid":"0000-0003-3350-9682","position":9,"is_corresponding":false},{"id":105442,"name":"Geoffrey Neale","orcid":"0000-0003-3776-0858","position":10,"is_corresponding":false},{"id":309089,"name":"Emily Walker","orcid":"0000-0003-4880-1483","position":11,"is_corresponding":false},{"id":109228,"name":"Hui Wang","orcid":"0000-0003-2791-8981","position":12,"is_corresponding":false},{"id":661422,"name":"Rachel Webster","orcid":"0000-0003-2173-5842","position":13,"is_corresponding":false},{"id":255615,"name":"Tara M. Brinkman","orcid":"0000-0002-4250-6160","position":14,"is_corresponding":false},{"id":230931,"name":"Kevin R. Krull","orcid":"0000-0002-0476-7001","position":15,"is_corresponding":false},{"id":230934,"name":"Gregory T. Armstrong","orcid":"0000-0001-8722-4207","position":16,"is_corresponding":false},{"id":255612,"name":"Kirsten K. Ness","orcid":"0000-0002-2084-1507","position":17,"is_corresponding":false},{"id":255630,"name":"Melissa M. Hudson","orcid":"0000-0001-6984-2407","position":18,"is_corresponding":false},{"id":342448,"name":"Qian Li","orcid":"0000-0001-9874-3555","position":19,"is_corresponding":false},{"id":255618,"name":"I‐Chan Huang","orcid":"0000-0002-1194-3923","position":20,"is_corresponding":false},{"id":255626,"name":"Zhaoming Wang","orcid":"0000-0001-7556-3869","position":21,"is_corresponding":false},{"id":1062238,"name":"Noel-Marie Plonski","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:06:46.330532Z","pmid":"38445706","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":[]}