Are racial disparities in colon cancer due to epigenetic outliers.

结肠癌的发病率和死亡率存在种族差异，其中非裔美国人最多。 阴性感染组。结肠癌对非裔美国人的不成比例影响可能是 归因于社会经济、环境和遗传因素。我们提议的研究将调查这种影响 表观遗传因素，受基因-环境相互作用的影响。我们的初步研究已经 确诊的结肠癌患者具有高度破坏的表观基因组，其特征是异常的部位特异性DNA 正常结肠黏膜中甲基化水平。“异常甲基化表型”个体的频率 与高加索人癌症患者相比，非裔美国人癌症患者的OMP增加。 我们不知道OMP状态对生存率的影响，因为在我们的初步研究中，OMP患者的数量 研究是有限的。然而，从两名癌症患者身上采集血液样本相对容易，侵入性也较小。 和健康的人，所以我们计划扩大我们在这一应用的初步研究。拟议的研究将 根据血液DNA中的甲基化水平确定OMP，并将确定非裔美国人是否在结肠 癌症患者OMPS的频率高于高加索人结肠癌患者，占 发病率和结局方面的种族差异。我们将分析70%~850K个CpG位点的甲基化水平 来自每个种族的健康和70名结肠癌患者。此外，OMP状态对生存和 使用特定于种族的表观遗传时钟的表观遗传老化也将被评估。后者将使我们能够研究 与非OMPS相比，OMPS中年龄相关的CPG是否更受干扰。我们预计我们的 这项研究将提供结肠癌种族差异的表观遗传学基础的证据。

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.