Are racial disparities in colon cancer due to epigenetic outliers.

结肠癌的种族差异是由于表观遗传异常值造成的吗？

• 批准号: 10304449
• 负责人: Jayashri Ghosh
• 金额: $ 22.23万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-16 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304449
• 关键词: Accounting; Affect; African American; Age; Aging; Biological Aging; Blood; Blood specimen; Cancer Etiology; Cancer Patient; Caucasians; Cessation of life; Chronology; Clinical; Colon; Colon Carcinoma; Colonoscopy; DNA; DNA Methylation; Data; Data Analyses; Data Set; Databases; Diet; Disease; Early Diagnosis; Environmental Risk Factor; Epigenetic Process; Exhibits; Frequencies; Genetic; High Prevalence; Incidence; Individual; Malignant Neoplasms; Methylation; Mucous Membrane; Normal tissue morphology; Outcome; Patients; Persons; Phenotype; Polyps; Population; Population Group; Race; Risk; Role; Sample Size; Screening procedure; Site; Socioeconomic Factors; Specificity; The Cancer Genome Atlas; Tissue Sample; Tissues; United States; Whole Blood; adverse outcome; age related; base; colon cancer patients; epigenome; epigenome-wide association studies; gene environment interaction; gut microbiome; mortality; negative affect; personalized medicine; prevent; racial difference; racial disparity; screening; socioeconomics

Racial disparities in the incidence and mortality of colon cancer exist, with African Americans being the most negatively affected group. The disproportionate impact of colon cancer on African Americans could be attributed to socioeconomic, environmental and genetic factors. Our proposed study will investigate the impact of epigenetic factors, which are influenced by gene-environment interactions. Our preliminary studies have identified colon cancer patients with highly disrupted epigenomes, characterized by abnormal site-specific DNA methylation levels in normal colon mucosa. The frequency of individuals with “Outlier Methylation Phenotype” (OMP) was found to be increased in African American cancer patients compared to Caucasian cancer patients. We do not know the effect of OMP status on survival because the number of OMP patients in our preliminary study is limited. However, it is relatively easy and less invasive to get blood samples from both cancer patients and healthy individuals, so we plan to expand our preliminary study in this application. The proposed study will identify OMPs based on methylation levels in blood DNA and will determine whether African Americans colon cancer patient have a higher frequency of OMPs compared to Caucasian colon cancer patients, accounting for racial disparities in incidence and outcome. We will analyze methylation levels at ~850K CpG sites in 70 healthy and 70 colon cancer patients from each race. Furthermore, the impact of OMP status on survival and epigenetic aging, using race-specific epigenetic clocks will also be evaluated. The latter will enable us to study whether or not age-related CpGs are more disrupted in OMPs compared to non-OMPs. We anticipate that our study will provide evidence of an epigenetic basis for racial disparities in colon cancer.

结肠癌的发病率和死亡率存在种族差异，非洲裔美国人最多， 受负面影响的群体。结肠癌对非裔美国人的不成比例的影响可能是 社会经济、环境和遗传因素。我们提出的研究将调查 表观遗传因素，这是受基因与环境的相互作用。我们的初步研究表明 确定了具有高度破坏的表观基因组的结肠癌患者，其特征在于异常的位点特异性DNA 正常结肠粘膜中的甲基化水平。具有“异常甲基化表型”的个体频率 (OMP)与白人癌症患者相比，非洲裔美国人癌症患者中的 我们不知道OMP状态对生存率的影响，因为我们的初步研究中OMP患者的数量 研究有限。然而，从这两种癌症患者身上获取血液样本相对容易，侵入性也较小 和健康的个体，所以我们计划扩大我们的初步研究在这个应用程序。拟定的研究将 根据血液DNA中的甲基化水平鉴定OMPs，并将确定非裔美国人结肠癌 与高加索结肠癌患者相比，癌症患者的OMP频率更高，占 发病率和结果的种族差异。我们将分析70例中~ 850 K CpG位点的甲基化水平， 健康人和来自每个种族的70名结肠癌患者。此外，OMP状态对生存率的影响， 表观遗传老化，使用种族特异性表观遗传时钟也将进行评估。后者将使我们能够研究 与非OMP相比，OMP中与年龄相关的CpG是否更容易被破坏。我们预计， 这项研究将为结肠癌的种族差异提供表观遗传学基础的证据。