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

肺癌是男性和女性癌症死亡的主要原因。非裔美国人（AAs） 肺癌的风险高于欧洲裔美国人（EAs）和美国的任何其他种族群体。 此外，社会经济上处于不利地位的人群患肺癌的负担高于其他人群。 我们最近发现，生活在贫困社区的AA男性有高达1.5倍的 肺癌的风险比生活在更好的社区的人要高。我们还发现健康饮食 与肺癌的低风险相关。然而，连接这些细胞的生物学机制 DNA甲基化是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中起着至关重要的作用。生活方式和社会经济 社会经济地位（SES）因素可能通过甲基化修饰AA影响健康， 富裕的人口。 社会经济 肺癌的发病因素尚不清楚。 .此外，SES 处境不利的人口承受着更大的生物老化加速。然而， 个人和 社会经济地位和生活方式因素 影响AA中的DNA甲基化、生物老化和肺癌风险， 社会经济弱势群体基本上不为人知。正在进行的国家癌症研究所资助的南方 社区队列研究（SCCS），一项具有里程碑意义的研究，跟踪了约86，000名成年人的队列，其中三分之二为AA 和三分之一的非西班牙裔EAs，显示出类似的低SES之间的AA和EA。建立在这些独特的 资源，我们将进行第一个强大的前瞻性社会表观基因组学研究的队列在一个 肺癌风险增加。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例肺癌病例（800例AA和450例EA）和1,700例个体匹配的对照（800例EA）。 AAs和900 EA）。使用这些甲基化数据，沿着在SCCS中收集的丰富的流行病学数据， 我们将：确定甲基化标记和模式与种族（自我报告和遗传 （一）个人和 社会 SES和生活方式因素（目的1），并进一步研究DNA是否 目标1中鉴定的甲基化标志物和模式与肺癌风险相关（目标2）;研究 生活方式和SES因素与生物衰老（甲基化年龄和年龄）之间的关联 加速）（目标3），并研究生物老化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功能进行体外功能研究。 调控基因由于详细的流行病学数据和生物样本已于2004年收集， 根据母公司的研究，这个拟议的项目既高度可行，又极具成本效益。时发现的问题 这项研究可能会深入了解 个人和社会背景因素 影响DNA甲基化， 更好地了解SES/生活方式因素与肺癌风险之间的机制关系。的 研究结果也可能提供有用的信息，可用于改善肺癌的差异。

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.