Individual and social contextual factors in relation to DNA methylation, biological aging, and lung cancer risk

与 DNA 甲基化、生物衰老和肺癌风险相关的个人和社会背景因素

• 批准号: 10600037
• 负责人: QIUYIN CAI
• 金额: $ 64.73万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-24 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10600037
• 关键词: Acceleration; Adult; Affect; African American population; Age; American; Bioinformatics; Biological; Biological Aging; Biological Assay; Biological Markers; Blood; Blood specimen; Cancer Etiology; Cell physiology; Cessation of life; Cigarette; Cohort Studies; Communities; Complement; DNA; DNA Methylation; Data; Diagnostic; Disparity population; Early Diagnosis; Eating; Economically Deprived Population; Education; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Ethnic Population; European; Funding; Gene Expression; Genes; Goals; Health; Healthy Eating; Histologic; Household; In Vitro; Income; Individual; Investigation; Life Style; Link; Malignant neoplasm of lung; Mental Depression; Methylation; Modification; Molecular; Neighborhoods; Not Hispanic or Latino; Occupational Status; Parents; Participant; Pathway interactions; Patient Self-Report; Play; Population; Race; Reporting; Resources; Risk; Risk Factors; Role; Sampling; Site; Smoking; Smoking and Health Research; Social Environment; Social support; Socioeconomic Factors; Socioeconomic Status; Stress; Testing; Time; Woman; cancer health disparity; cancer risk; cigarette smoking; cohort; contextual factors; cost efficient; deprivation; epidemiologic data; epigenomics; genome wide methylation; genome-wide; high risk; indexing; innovation; insight; lifestyle factors; low socioeconomic status; lung cancer screening; male; men; methylation biomarker; methylation pattern; prospective; racial disparity; racial minority; racial population; social; social factors; socioeconomic disadvantage; socioeconomic disparity

Lung cancer is the leading cause of cancer death in both men and women. African Americans (AAs) have a higher risk of lung cancer than European Americans (EAs) and any other racial group in the U.S. In addition, socioeconomically disadvantaged populations suffer a higher burden of lung cancer than more We recently found that AA males living in deprived neighborhoods had up to a 1.5-fold increased risk of lung cancer than those living in better neighborhoods. We also found that healthy eating was associated with a lower risk of lung cancer. However, the biological mechanisms linking the DNA methylation, one of the most frequent and important epigenetic modifications, plays a crucial role in regulating gene expression and cell function. Lifestyle and socioeconomic status (SES) factors may affect health through methylation modifications AAs and affluent populations. socioeconomic factors with lung cancer is not clear. . In addition, SES disadvantaged populations endure a greater acceleration of biological aging. However, how the individual and social SES and lifestyle factors affect DNA methylation, biological aging, and lung cancer risk in AAs and socioeconomically disadvantaged populations is largely unknown. The ongoing NCI-funded Southern Community Cohort Study (SCCS), a landmark investigation tracking a cohort of ~86,000 adults, two-thirds AAs and one-third non-Hispanic EAs, shows a similar low SES among AAs and EAs. Building on these unique resources, we will conduct the first well-powered prospective social epigenomics study in a cohort at an elevated lung cancer risk. We will perform genome-wide methylation assays for pre-diagnostic blood samples from 1,250 incident lung cancer cases (800 AAs and 450 EAs) and 1,700 individually-matched controls (800 AAs and 900 EAs). Using these methylation data, along with rich epidemiological data collected in the SCCS, we will: identify methylation markers and patterns in association with race (self-reported and genetically determined), individual and social SES, and lifestyle factors (Aim 1) and further investigate whether DNA methylation markers and patterns identified in Aim 1 are associated with lung cancer risk (Aim 2); investigate the associations between lifestyle and SES factors with biological aging (methylation-based age and age acceleration) (Aim 3) and investigate whether biological aging is associated with lung cancer risk (Aim 4). We will further investigate the potential effect of SES and lifestyle factor changes on DNA methylation and biological aging. We will also conduct in vitro functional investigation of promising methylation sites and their regulated genes. Because detailed epidemiological data and biological samples have already been collected in the parent study, this proposed project is both highly feasible and extremely cost-efficient. Findings from this study may provide insights into how individual and social contextual factors affect DNA methylation and help us to better understand the mechanistic relationships between SES/lifestyle factors and lung cancer risk. The findings may also provide useful information which could be used to ameliorate the lung cancer disparities.

肺癌是男性和女性癌症死亡的主要原因。非裔美国人 (AA) 与欧洲裔美国人 (EA) 和美国任何其他种族群体相比，他们患肺癌的风险更高 此外，社会经济弱势群体的肺癌负担比其他群体更高 我们最近发现生活在贫困社区的 AA 男性的死亡率高达 1.5 倍 与生活在较好社区的人相比，患肺癌的风险更高。我们还发现健康饮食 与较低的肺癌风险相关。然而，将这些因素联系起来的生物学机制 DNA甲基化是最常见和最重要的表观遗传之一 修饰，在调节基因表达和细胞功能中起着至关重要的作用。生活方式和社会经济 状态（SES）因素可能通过甲基化修饰 AA 和 富裕人口。 社会经济的 与肺癌发生的因素尚不清楚。 。此外，SES 弱势群体的生物衰老速度加快。然而，如何 个人和 社会社会经济地位和生活方式因素 影响 AA 中的 DNA 甲基化、生物衰老和肺癌风险 社会经济弱势群体的情况在很大程度上是未知的。正在进行的由 NCI 资助的南方 社区队列研究 (SCCS) 是一项具有里程碑意义的调查，追踪了约 86,000 名成年人（其中三分之二为 AA）的队列 和三分之一的非西班牙裔 EA 在 AA 和 EA 中显示出类似的低 SES。建立在这些独特的 资源，我们将在一个队列中进行第一个强有力的前瞻性社会表观基因组学研究 肺癌风险升高。我们将对诊断前的血液样本进行全基因组甲基化检测 来自 1,250 个肺癌病例（800 个 AA 和 450 个 EA）和 1,700 个单独匹配的对照（800 个 AA 和 900 个 EA）。利用这些甲基化数据以及 SCCS 中收集的丰富流行病学数据， 我们将： 识别与种族相关的甲基化标记和模式（自我报告和遗传基因） 确定），个人和 社会的 SES 和生活方式因素（目标 1）并进一步调查 DNA 是否 目标 1 中确定的甲基化标记物和模式与肺癌风险相关（目标 2）；调查 生活方式和SES因素与生物衰老之间的关联（基于甲基化的年龄和年龄 加速）（目标 3）并研究生物衰老是否与肺癌风险相关（目标 4）。我们 将进一步研究SES和生活方式因素变化对DNA甲基化的潜在影响 生物老化。我们还将对有希望的甲基化位点及其它们进行体外功能研究 调控基因。因为详细的流行病学数据和生物样本已经在 根据母研究，该拟议项目既高度可行，又极具成本效益。由此得出的结论 研究可能会提供关于如何 个人和社会背景因素 影响DNA甲基化并帮助我们 更好地了解 SES/生活方式因素与肺癌风险之间的机制关系。这 研究结果还可能提供有用的信息，可用于改善肺癌的差异。

项目成果

Pre-diagnostic circulating p53 autoantibodies and subsequent lung cancer risk in low-income African and European Americans.

低收入非洲裔和欧洲裔美国人的诊断前循环 p53 自身抗体和随后的肺癌风险。

• DOI: 10.1016/j.canep.2022.102288
• 发表时间: 2022
• 期刊: Cancer epidemiology
• 影响因子: 2.6
• 作者: Yoon,Hyung-Suk;Zheng,Wei;Cai,Hui;Wu,Jie;Shidal,Chris;Wang,Jifeng;Shu,Xiao-Ou;Waterboer,Tim;Blot,WilliamJ;Cai,Qiuyin
• 通讯作者: Cai,Qiuyin