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，其中非洲裔美国人最为严重 结肠癌对非裔美国人的负面影响可能是不成比例的。 我们提出的研究将调查其影响。 我们的初步研究表明，表观遗传因素受到基因与环境相互作用的影响。 鉴定出具有高度破坏的表观基因组的结肠癌患者，其特征是异常的位点特异性 DNA 正常结肠粘膜中的甲基化水平具有“异常甲基化表型”的个体的频率。 研究发现，与白人癌症患者相比，非裔美国癌症患者的 OMP 水平有所增加。 我们不知道 OMP 状态对生存的影响，因为我们初步研究中 OMP 患者的数量 然而，从两名癌症患者身上获取血液样本相对容易且侵入性较小。 和健康个体，因此我们计划扩大我们在该应用中的初步研究。 根据血液 DNA 中的甲基化水平识别 OMP，并将确定非裔美国人是否患有结肠癌 与白人结肠癌患者相比，癌症患者的 OMP 频率更高，占 我们将分析 70 个国家中约 850K CpG 位点的甲基化水平。 每个种族的健康人和 70 名结肠癌患者。此外，OMP 状态对生存和生存的影响 表观遗传衰老，使用种族特异性表观遗传时钟也将被评估，后者将使我们能够进行研究。 与非 OMP 相比，OMP 中与年龄相关的 CpG 是否受到更多干扰。 研究将为结肠癌种族差异的表观遗传基础提供证据。