Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age-related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation-based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array-based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self-reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = −0.25, 95% confidence interval (−0.32, −0.18), p = 1.48E-12]. Greater value of VACS Index [beta = −0.002 (−0.003, −0.001), p = 2.82E-05] and higher cancer prevalence [beta = −0.07 (−0.10, −0.03), p = 1.37E-04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E-03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all-cause mortality.

中文翻译：

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基于 DNA 甲基化的端粒长度与 HIV 感染、身体虚弱、癌症和全因死亡率相关

端粒长度（TL）是细胞衰老的重要指标。较短的 TL 与多种与年龄相关的疾病有关，包括冠心病、心力衰竭、糖尿病、骨质疏松症和癌症。最近，基于 DNA 甲基化的 TL (DNAmTL) 估计器已被开发出来，作为直接测量 TL 的替代方法。在这项研究中，我们在退伍军人衰老队列研究生物标志物队列 (VACS, N  = 1917) 和妇女机构间 HIV 研究队列 (WIHS, N  = 481)中检查了 DNAmTL 与感染和未感染 HIV 的人群中癌症患病率和死亡风险的关联。。我们使用基于阵列的方法对全血 (VACS) 或外周血单核细胞 (WIHS) 中的 DNAm 进行了分析。癌症患病率是根据电子病历和癌症登记数据估计的。 VACS 指数被用来衡量生理虚弱程度。模型根据自我报告的种族和民族、批次、吸烟状况、饮酒情况和五种细胞类型（CD4、CD8、NK、B 细胞和单核细胞）进行调整。我们发现 HIV 感染者的平均 DNAmTL 比未感染 HIV 的人短 [beta = -0.25, 95% 置信区间 (-0.32, -0.18), p  = 1.48E-12]。 VACS 指数值更大 [beta = -0.002 (-0.003, -0.001), p  = 2.82E-05] 和更高的癌症患病率 [beta = -0.07 (-0.10, -0.03), p  = 1.37E-04，无需调整年龄]与缩短的 DNAmTL 相关。此外，DNAmTL 减少 1 KB 与死亡风险增加 40% 相关 [风险比：0.60 (0.44, 0.82)，p  = 1.42E-03]。总之，HIV 感染、生理虚弱和癌症与 DNAmTL 缩短有关，导致全因死亡风险增加。