■目前对表观遗传年龄加速(EAA)的研究仅限于非西班牙裔白人个体。必须通过在EAA研究中考虑种族和少数民族来提高包容性。
■通过检查EAA与癌症治疗暴露的关联,比较非西班牙裔黑人与非西班牙裔白人儿童癌症幸存者,EAA中潜在的种族和民族差异,以及健康的社会决定因素(SDOH)的中介作用。
■在这项横断面研究中,参与者来自圣裘德终身队列,该项目始于2007年,正在进行后续行动。符合条件的参与者包括1962年至2012年在圣裘德儿童研究医院接受治疗的非西班牙裔黑人和非西班牙裔白人儿童癌症幸存者,他们有DNA甲基化数据。数据分析于2023年2月至2024年5月进行。
■儿童癌症的三种治疗暴露(胸部放疗,烷化剂,和表鬼臼毒素)。
■从外周血单核细胞来源的DNA产生DNA甲基化。EAA计算为根据实际年龄回归Levine或Horvath表观遗传年龄的残差。SDOH包括教育程度,个人年收入,和社会经济区剥夺指数(ADI)。一般线性模型评估了EAA与种族和种族(非西班牙裔黑人和非西班牙裔白人)和/或SDOH的横截面关联,适应性,身体质量指数,吸烟,和癌症治疗。计算EAA的调整最小二乘均值(ALSM)用于组比较。中介分析将SDOH视为具有平均因果中介效应(ACME)的介体,计算了EAA与种族和种族的关联。
■在总共1706名幸存者中,包括230名非西班牙裔黑人幸存者(诊断时的中位[IQR]年龄,9.5[4.3-14.3]岁;103名男性[44.8%]和127名女性[55.2%])和1476名非西班牙裔白人幸存者(诊断时的中位[IQR]年龄,9.3[3.9-14.6]岁;766名男性[51.9%]和710名女性[48.1%]),非西班牙裔黑人幸存者(ALSM=1.41;95%CI,0.66至2.16)的EAA明显高于非西班牙裔白人幸存者(ALSM=0.47;95%CI,0.12至0.81)。在非西班牙裔黑人幸存者中,接受胸部放疗的患者(ALSM=2.82;95%CI,1.37至4.26)与未接触者(ALSM=0.46;95%CI,-0.60至1.51)相比,EAA显着增加,在那些暴露于烷化剂(ALSM=2.33;95%CI,1.21至3.45)与那些未暴露(ALSM=0.95;95%CI,-0.38至2.27),以及暴露于表鬼臼毒素的人群(ALSM=2.83;95%CI,1.27~4.40)与未暴露人群(ALSM=0.44;95%CI,-0.52~1.40)。EAA与表鬼臼毒素的关联因种族和种族而异(非西班牙裔黑人幸存者的β,2.39年;95%CI,0.74至4.04年;非西班牙裔白人幸存者的β,0.68;95%CI,0.05~1.31年),差异显著(1.77年;95%CI,0.01~3.53年;交互作用P=0.049)。EAA中的种族和种族差异是由教育程度介导的(<高中vs≥大学,ACME=0.13;高中与大学,ACME=0.07;调解=22.71%)和ADI(ACME=0.24;调解=22.16%)。
■在这项针对儿童癌症幸存者的横断面研究中,种族和民族缓和了EAA与表鬼臼毒素暴露的关联,EAA的种族和民族差异部分由教育程度和ADI介导,表明种族和民族的不同治疗毒性作用。这些发现表明,改善社会支持系统可以减轻与更大的加速衰老相关的社会经济劣势,并减少儿童癌症幸存者之间的健康差距。
UNASSIGNED: Current research in epigenetic age acceleration (EAA) is limited to non-Hispanic White individuals. It is imperative to improve inclusivity by considering racial and ethnic minorities in EAA research.
UNASSIGNED: To compare non-Hispanic Black with non-Hispanic White survivors of childhood cancer by examining the associations of EAA with cancer treatment exposures, potential racial and ethnic disparity in EAA, and mediating roles of social determinants of health (SDOH).
UNASSIGNED: In this cross-sectional study, participants were from the St Jude Lifetime Cohort, which was initiated in 2007 with ongoing follow-up. Eligible participants included non-Hispanic Black and non-Hispanic White survivors of childhood cancer treated at St Jude Children\'s Research Hospital between 1962 and 2012 who had DNA methylation data. Data analysis was conducted from February 2023 to May 2024.
UNASSIGNED: Three treatment exposures for childhood cancer (chest radiotherapy, alkylating agents, and epipodophyllotoxin).
UNASSIGNED: DNA methylation was generated from peripheral blood mononuclear cell-derived DNA. EAA was calculated as residuals from regressing Levine or Horvath epigenetic age on chronological age. SDOH included educational attainment, annual personal income, and the socioeconomic area deprivation index (ADI). General linear models evaluated cross-sectional associations of EAA with race and ethnicity (non-Hispanic Black and non-Hispanic White) and/or SDOH, adjusting for sex, body mass index, smoking, and cancer treatments. Adjusted least square means (ALSM) of EAA were calculated for group comparisons. Mediation analysis treated SDOH as mediators with average causal mediation effect (ACME) calculated for the association of EAA with race and ethnicity.
UNASSIGNED: Among a total of 1706 survivors including 230 non-Hispanic Black survivors (median [IQR] age at diagnosis, 9.5 [4.3-14.3] years; 103 male [44.8%] and 127 female [55.2%]) and 1476 non-Hispanic White survivors (median [IQR] age at diagnosis, 9.3 [3.9-14.6] years; 766 male [51.9%] and 710 female [48.1%]), EAA was significantly greater among non-Hispanic Black survivors (ALSM = 1.41; 95% CI, 0.66 to 2.16) than non-Hispanic White survivors (ALSM = 0.47; 95% CI, 0.12 to 0.81). Among non-Hispanic Black survivors, EAA was significantly increased among those exposed to chest radiotherapy (ALSM = 2.82; 95% CI, 1.37 to 4.26) vs those unexposed (ALSM = 0.46; 95% CI, -0.60 to 1.51), among those exposed to alkylating agents (ALSM = 2.33; 95% CI, 1.21 to 3.45) vs those unexposed (ALSM = 0.95; 95% CI, -0.38 to 2.27), and among those exposed to epipodophyllotoxins (ALSM = 2.83; 95% CI, 1.27 to 4.40) vs those unexposed (ALSM = 0.44; 95% CI, -0.52 to 1.40). The association of EAA with epipodophyllotoxins differed by race and ethnicity (β for non-Hispanic Black survivors, 2.39 years; 95% CI, 0.74 to 4.04 years; β for non-Hispanic White survivors, 0.68; 95% CI, 0.05 to 1.31 years) and the difference was significant (1.77 years; 95% CI, 0.01 to 3.53 years; P for interaction = .049). Racial and ethnic disparities in EAA were mediated by educational attainment (
UNASSIGNED: In this cross-sectional study of childhood cancer survivors, race and ethnicity moderated the association of EAA with epipodophyllotoxin exposure and racial and ethnic differences in EAA were partially mediated by educational attainment and ADI, indicating differential treatment toxic effects by race and ethnicity. These findings suggest that improving social support systems may mitigate socioeconomic disadvantages associated with even greater accelerated aging and reduce health disparities among childhood cancer survivors.