Department of Public Health and Community Medicine, Tufts University School of Medicine, Tufts University, Boston, MA 02111, USA.
Division of Nutrition Epidemiology and Data Science, Friedman School of Nutrition, Tufts University, Boston, MA 02111, USA.
Aging (Albany NY). 2023 Feb 7;15(3):617-629. doi: 10.18632/aging.204501.
Epigenetic age, a robust marker of biological aging, has been associated with obesity, low-grade inflammation and metabolic diseases. However, few studies have examined associations between different epigenetic age measures and risk of lung cancer, despite great interest in finding biomarkers to assist in risk stratification for lung cancer screening.
A nested case-control study of lung cancer from the CLUE II cohort study was conducted using incidence density sampling with 1:1 matching of controls to lung cancer cases ( = 208 matched pairs). Prediagnostic blood samples were collected in 1989 (CLUE II study baseline) and stored at -70°C. DNA was extracted from buffy coat and DNA methylation levels were measured using Illumina MethylationEPIC BeadChip Arrays. Three epigenetic age acceleration (i.e., biological age is greater than chronological age) measurements (Horvath, Hannum and PhenoAge) were examined in relation to lung cancer risk using conditional logistic regression.
We did not observe associations between the three epigenetic age acceleration measurements and risk of lung cancer overall; however, inverse associations for the two Hannum age acceleration measures (intrinsic and extrinsic) were observed in men and among younger participants, but not in women or older participants. We did not observe effect modification by time from blood draw to diagnosis.
Findings from this study do not support a positive association between three different biological age acceleration measures and risk of lung cancer. Additional studies are needed to address whether epigenetic age is associated with lung cancer in never smokers.
表观遗传年龄是生物学年龄的一个强有力的标志物，与肥胖、低度炎症和代谢性疾病有关。然而，尽管人们对寻找有助于肺癌筛查风险分层的生物标志物非常感兴趣，但很少有研究探讨不同的表观遗传年龄测量值与肺癌风险之间的关系。
使用 CLUE II 队列研究中的发病率密度抽样，对肺癌进行了一项巢式病例对照研究，对病例（=208 对匹配）进行了 1:1 匹配对照。在 1989 年（CLUE II 研究基线）采集了前瞻性血样，并在-70°C 下储存。从白细胞层中提取 DNA，并使用 Illumina MethylationEPIC BeadChip 阵列测量 DNA 甲基化水平。使用条件逻辑回归分析了三种表观遗传年龄加速（即生物年龄大于实际年龄）测量值（Horvath、Hannum 和 PhenoAge）与肺癌风险之间的关系。
我们没有观察到这三种表观遗传年龄加速测量值与肺癌总体风险之间的关联；然而，在男性和较年轻的参与者中，Hannum 年龄加速的两个测量值（内在和外在）与肺癌风险呈负相关，但在女性或年龄较大的参与者中则不然。我们没有观察到从采血到诊断的时间对效应的修饰作用。
这项研究的结果不支持三种不同的生物年龄加速测量值与肺癌风险之间存在正相关关系。需要进一步的研究来确定表观遗传年龄是否与从不吸烟者的肺癌有关。
