Reducing racial disparities in lung cancer outcomes by decoding neighborhood contextual environment (RECODE)

通过解码邻里环境来减少肺癌结果的种族差异 (RECODE)

• 批准号: 10402245
• 负责人: Sage J. Kim
• 金额: $ 65.59万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-06 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10402245
• 关键词: Affect; African American; African American population; Area; Arginine; Behavioral; Biological; Biophysics; Black American; Black Populations; Cancer Etiology; Censuses; Cessation of life; ChIP-seq; Characteristics; Chicago; Chronic; Chronic stress; Cities; Clinical Trials; Communities; Computerized Medical Record; Cotinine; Crime; Data; Data Collection; Data Set; Disadvantaged; Distress; Economics; Environment; Environmental Risk Factor; Epigenetic Process; Epithelial; Exposure to; Frequencies; Gene Expression; Hair; Hydrocortisone; Immunohistochemistry; Incidence; Individual; Inflammatory Response; Link; Low Prevalence; Lung; Lung Neoplasms; Malignant neoplasm of lung; Measures; Mediating; Methylation; Molecular; Morbidity - disease rate; Mus; Neighborhoods; Outcome; Patients; Physiological; Population; Protein Overexpression; Proteins; Research; Risk; Risk Factors; Sampling; Smoking; Smoking History; Social Conditions; Source; Stage at Diagnosis; Stress; Surveys; Testing; The Cancer Genome Atlas; Time; Tissue Sample; Transferase; United States; Violence; base; biobank; black men; cancer health disparity; cancer risk; cigarette smoking; contextual factors; high risk; improved; in silico; innovation; lung cancer screening; men; minority communities; mortality; novel; overexpression; prospective; protein expression; racial disparity; racial health disparity; racial minority; screening; screening guidelines; smoking exposure; social; social stress; social stressor; sociodemographics; socioenvironmental factor; systemic inflammatory response; transcriptome sequencing; violence exposure; violent crime

ABSTRACT This application proposes to examine a novel social epigenetic mechanism for racial inequality in lung cancer: Reducing racial disparities in lung cancer outcomes by decoding neighborhood contextual environment (RECODE). We will examine the relationships between exposure to violence, inflammatory responses, smoking and epigenetic changes in protein arginine methyl transferases (PRMT6) that increase the risk of developing lung cancer. Our preliminary studies demonstrated that smoking induces increased expression of PRMT6 in the lung epithelium. We also showed that overexpression of PRMT6 triggers spontaneous lung tumors in mice. Interestingly, we found that PRMT6 is upregulated among black men compared with white men in The Cancer Genome Atlas (TCGA). Thus we argue that the increased overexpression of PRMT6 among black men may explain a higher rate of lung cancer among black men compared with white men. While smoking is a key contributing factor for lung cancer, the frequency and amount of cigarette smoking are not necessarily higher for blacks, which suggests that other factors are responsible for racial disparity in lung cancer. Disproportionate social stress in black communities may be responsible for a higher rate of lung cancer among blacks. In particular, individuals living in excessive neighborhood violence are exposed to chronic stress, which may intensify the epigenetic changes for lung cancer. We hypothesize that exposure to neighborhood violence is social stress that increases biophysical inflammatory responses, which exacerbate the path between smoking, PRMT6 overexpression, and lung cancer. To examine the proposed social epigenetic mechanism of lung cancer disparity, first, we will test the independent effect of smoking and exposure to neighborhood violence, and the interaction of the two risks on PRMT6 expression using retrospective tissue samples from black and white lung cancer cases (Aim 2). Second, we will test the effect of exposure to violence on an inflammatory response (hair cortisol) and lung cancer screening outcomes by conducting a prospective survey and data collection with high-risk black men (Aim 3). Finally, we will build a multilevel, context-specific lung cancer risk profiles (Aim 1) that take into account not only individual behavioral risk (smoking), but neighborhood stress (exposure to violence), physiological inflammatory responses (increased cortisol), and molecular changes (PRMT6 overexpression). To develop such risk profiles, we utilize a composite population data approach to establish accurate counts of all individuals within census tracts with sociodemographic, behavioral, and neighborhood risk profiles. The strength of RECODE is its innovative approach to unveil a social epigenetic mechanism of lung cancer disparity. RECODE has the potential to transform understanding multilevel risks of lung cancer and improve the national lung cancer screening guidelines to reflect the social conditions of racial minority communities.

抽象的 该应用建议检查一种新型的肺癌种族不平等社会表观遗传机制： 通过解码邻里环境环境来减少肺癌结局的种族差异 （recode）。我们将研究暴露暴力，炎症反应， 蛋白质精氨酸转移酶（PRMT6）的吸烟和表观遗传变化增加了 发展肺癌。我们的初步研究表明，吸烟引起了增加的表达 肺上皮中的PRMT6。我们还表明，PRMT6的过表达触发自发肺 小鼠的肿瘤。有趣的是，我们发现PRMT6与白色相比在黑人中被上调 癌症基因组地图集（​​TCGA）中的男性。因此，我们认为PRMT6的过表达增加 在黑人中，与白人相比，黑人男性的肺癌发生率更高。尽管 吸烟是导致肺癌的关键因素，吸烟的频率和数量不是 黑人必然会更高，这表明其他因素是肺部种族差异的原因 癌症。黑人社区中的社会压力不成比例，可能是较高的肺部 黑人中的癌症。特别是，居住在邻里过度暴力的个人暴露于 慢性应激，这可能会加剧肺癌的表观遗传变化。我们假设接触 邻里暴力是社会压力，会增加生物物理炎症反应，这加剧了 吸烟，PRMT6过表达和肺癌之间的路径。 为了检查拟议的肺癌差异的社会表观遗传机制，首先，我们将测试 吸烟和暴露于邻里暴力的独立影响，以及两种风险的相互作用 PRMT6使用来自黑白肺癌病例的回顾性组织样品表达（AIM 2）。 其次，我们将测试暴露暴力对炎症反应（皮质醇）和肺的影响 通过高危黑人进行前瞻性调查和数据收集，进行癌症筛查结果 （目标3）。最后，我们将建立一个多级，特定于上下文的肺癌风险概况（AIM 1） 不仅说明个人行为风险（吸烟），还包括邻里压力（暴露暴力）， 生理炎症反应（皮质醇增加）和分子变化（PRMT6过表达）。 为了开发这种风险概况，我们利用一种复合人口数据方法来确定 人口普查中的所有个人都具有社会人口统计学，行为和邻里风险概况。 recode的强度是其创新的方法来揭示肺癌的社会表观遗传机制 差距。 recode有可能改变理解肺癌的多层次风险并改善 国家肺癌筛查指南，以反映少数民族社区的社会状况。