Biological Aging Measures Based on Blood DNA Methylation and Risk of Cancer: A Prospective Study.
Biological Aging Measures Based on Blood DNA Methylation and Risk of Cancer: A Prospective Study.
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DOI：
10.1093/jncics/pkaa109
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发表时间：
2021-03
影响因子：
4.4
通讯作者：
Milne RL
中科院分区：
文献类型：
--
作者：
Dugué PA;Bassett JK;Wong EM;Joo JE;Li S;Yu C;Schmidt DF;Makalic E;Doo NW;Buchanan DD;Hodge AM;English DR;Hopper JL;Giles GG;Southey MC;Milne RL
我们之前在墨尔本合作队列研究中调查了表观遗传老化的5个“第一代”指标与癌症风险之间的关联。这项研究评估了最近开发的3种基于甲基化的衰老生物标志物的癌症风险相关性：PhenoAge、Grimage和预测的端粒长度。我们使用条件Logistic回归模型估计了这3项年龄调整指标与结直肠癌(N = 813)、胃癌(N = 165)、肾脏(N = 139)、肺癌(N = 327)、成熟B细胞(N = 423)、前列腺癌(N = 846)和尿路上皮癌(N = 404)风险的比率比(RR)。我们还评估了自抽血以来的时间和癌症亚型的相关性，并调查了潜在的非线性。我们观察到，年龄调整后的表观年龄与结直肠癌、肾癌、肺癌、成熟B细胞癌和尿路上皮癌的风险有较强的相关性(每标准差的相对危险度约为1.2-1.3)。在年龄调整的朝圣中也得到了类似的结果，但在调整了吸烟状况、吸烟年限、开始年龄、戒烟时间和其他癌症危险因素后，与肺癌风险的关联要大得多(每标准差 = 为1.82，95%可信区间[CI] = 为1.44至2.3)。大多数相关性似乎是线性的，比第一代测量的要大，在对一大组社会人口、生活方式和人体测量变量进行调整后，几乎没有变化。总体而言，综合调整后的每标准差比为1.13(95%CI = 1.07~1.19)和1.12(95%CI = 1.05~1.2 0)，且在采血后5 年内出现较大值(RR = 1.29，95%CI = 1.15~1.44和1.19，95%CI = 1.06~1.33)。基于甲基化的指标PhenoAge和Grimage可能为生物衰老和癌症之间的关系提供洞察力，并有助于预测癌症风险，特别是肺癌风险。
We previously investigated the association between 5 “first-generation” measures of epigenetic aging and cancer risk in the Melbourne Collaborative Cohort Study. This study assessed cancer risk associations for 3 recently developed methylation-based biomarkers of aging: PhenoAge, GrimAge, and predicted telomere length. We estimated rate ratios (RRs) for the association between these 3 age-adjusted measures and risk of colorectal (N = 813), gastric (N = 165), kidney (N = 139), lung (N = 327), mature B-cell (N = 423), prostate (N = 846), and urothelial (N = 404) cancer using conditional logistic regression models. We also assessed associations by time since blood draw and by cancer subtype, and we investigated potential nonlinearity. We observed relatively strong associations of age-adjusted PhenoAge with risk of colorectal, kidney, lung, mature B-cell, and urothelial cancers (RR per SD was approximately 1.2-1.3). Similar findings were obtained for age-adjusted GrimAge, but the association with lung cancer risk was much larger (RR per SD = 1.82, 95% confidence interval [CI] = 1.44 to 2.30), after adjustment for smoking status, pack-years, starting age, time since quitting, and other cancer risk factors. Most associations appeared linear, larger than for the first-generation measures, and were virtually unchanged after adjustment for a large set of sociodemographic, lifestyle, and anthropometric variables. For cancer overall, the comprehensively adjusted rate ratio per SD was 1.13 (95% CI = 1.07 to 1.19) for PhenoAge and 1.12 (95% CI = 1.05 to 1.20) for GrimAge and appeared larger within 5 years of blood draw (RR = 1.29, 95% CI = 1.15 to 1.44 and 1.19, 95% CI = 1.06 to 1.33, respectively). The methylation-based measures PhenoAge and GrimAge may provide insights into the relationship between biological aging and cancer and be useful to predict cancer risk, particularly for lung cancer.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
5.2
作者：
Kresovich, Jacob K.;Xu, Zongli;Taylor, Jack A.
通讯作者：
Taylor, Jack A.
影响因子：
5.7
作者：
Eilers, PHC;Marx, BD
通讯作者：
Marx, BD
DOI：
10.1016/b978-0-12-812215-0.00003-0
发表时间：
2018-01-01
期刊：
EPIGENETICS IN HUMAN DISEASE, 2ND EDITION
影响因子：
--
作者：
Dugue, Pierre-Antoine;Li, Shuai;Milne, Roger L.
通讯作者：
Milne, Roger L.