Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.
Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA.
J Natl Cancer Inst. 2024 Jul 1;116(7):1116-1125. doi: 10.1093/jnci/djae046.
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.
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.
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.
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.
儿童癌症幸存者面临较高的发病率和死亡率，以及较差的患者报告结局，通常是健康相关的生活质量（HRQOL）。然而，基于 DNA 甲基化的衰老生物标志物与 HRQOL 之间的关联尚未得到评估。
使用 Infinium EPIC BeadChip 在血液衍生的 DNA 上生成 DNA 甲基化（采血时年龄中位数=34.5 岁，范围为 18.5-66.6 岁），并使用来自 2206 名圣裘德终身队列幸存者的调查时年龄（平均=32.3 岁，范围为 18.4-64.5 岁）评估 HRQOL。基于 DNA 甲基化的衰老生物标志物，包括使用多个时钟（例如 GrimAge）和其他方法（例如 DNAmB2M：β-2-微球蛋白；DNAmADM：肾上腺髓质素）计算的表观遗传年龄，这些方法均来自于 DNAm Age Calculator（https://dnamage.genetics.ucla.edu）。使用医疗结果研究 36 项简短健康调查评估 HRQOL，以捕获 8 个领域和身体与精神成分综合评分。在调整采血时年龄、性别、癌症治疗以及吸烟包年数的 DNA 甲基化替代指标后，使用一般线性模型评估 HRQOL 与表观遗传年龄加速（EAA；例如，EAA_GrimAge）或其他年龄调整的基于 DNA 甲基化的生物标志物（例如，ageadj_DNAmB2M）之间的关联。所有 P 值均为双侧。
较差的 HRQOL 与更大的 EAA_GrimAge（身体成分综合评分：β=-0.18 岁，95%置信区间[CI]：-0.251 至-0.11 岁；P=1.85×10-5；以及 4 个 HRQOL 单项评分）、ageadj_DNAmB2M（身体成分综合评分：β=-0.08 岁，95%CI：-0.124 至-0.037 岁；P=0.003；以及 3 个 HRQOL 单项评分）和 ageadj_DNAmADM（身体成分综合评分：β=-0.082 岁，95%CI：-0.125 至-0.039 岁；P=0.002；以及 2 个 HRQOL 单项评分）相关。EAA_Hannum（Hannum 时钟）与任何 HRQOL 均无关。
总体和特定领域的 HRQOL 指标与生物衰老的 DNA 甲基化指标相关。未来的纵向研究应该检验生物衰老是否是 HRQOL 较差与临床评估的不良健康结果风险增加之间关联的潜在机制。
