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: 10306010
• 负责人: QIUYIN CAI
• 金额: $ 64.74万
• 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/10306010
• 关键词: Acceleration; Adult; Affect; African American; Age; American; Bioinformatics; Biological; Biological Aging; Biological Assay; Blood; Blood specimen; Cancer Etiology; Cell physiology; Cessation of life; Cigarette; Cohort Studies; Communities; Complement; DNA; DNA Methylation; Data; Diagnostic; Early Diagnosis; Eating; Education; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Ethnic group; 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 support; Socioeconomic Factors; Socioeconomic Status; Stress; Testing; Time; Woman; base; biomarker identification; cancer health disparity; cancer risk; cigarette smoking; cohort; contextual factors; cost efficient; deprivation; disadvantaged population; 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; 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.

肺癌是导致男性和女性癌症死亡的主要原因。非裔美国人(AA) 患肺癌的风险比欧洲裔美国人(EAs)和美国其他任何种族都要高。 此外，社会经济上处于不利地位的人群患肺癌的负担比 我们最近发现，生活在贫困社区的再生障碍性贫血男性的发病率是 与居住在较好社区的人相比，患肺癌的风险更高。我们还发现，健康饮食是 与较低的肺癌风险有关。然而，连接这些基因的生物机制 DNA甲基化，最常见和最重要的表观遗传学之一 修饰在调节基因表达和细胞功能方面起着至关重要的作用。生活方式与社会经济 状态(SES)因素可能通过甲基化修饰AAS和 富裕的人群。 社会经济学 肺癌的致病因素尚不清楚。 。此外，经济局局长 处于不利地位的人口承受着更大的生物老龄化加速。然而，如何 个人和 社会自尊与生活方式因素 影响DNA甲基化、生物老化和肺癌风险 社会经济上处于不利地位的人口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)，这是一项里程碑式的调查，跟踪了约86,000名成年人，三分之二的AA 三分之一的非西班牙裔欧洲人，在美国人和欧洲人中显示出类似的低SES。建立在这些独特的基础上 资源，我们将在一个队列中进行第一个强大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分析 来自1250例肺癌病例(800例AA和450例EA)和1700例单独配对的对照(800例 AAS和900个EAS)。使用这些甲基化数据，以及在SCCS中收集的丰富流行病学数据， 我们将：确定与种族相关的甲基化标记和模式(自我报告和遗传 决心)、个人和 社交 和生活方式因素(目标1)，并进一步调查DNA 目标1中确定的甲基化标记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(基于甲基化的年龄和年龄)的关系 加速)(目标3)，并调查生物老龄化是否与肺癌风险有关(目标4)。我们 将进一步研究SES和生活方式因素变化对DNA甲基化和 生物老化。我们还将进行体外甲基化位点和它们的功能研究 受调控的基因。因为详细的流行病学数据和生物样本已经在 在母公司的研究中，这一拟议项目既具有很高的可行性，又具有极高的成本效益。由此得出的结论 研究可能会为我们提供关于 个人和社会背景因素 影响DNA甲基化并帮助我们 为了更好地了解SES/生活方式因素与肺癌风险之间的机制关系。这个 研究结果也可能提供有用的信息，可以用来改善肺癌的差异。