Study of the Oral Microbiome to Address Racial Disparities in Esophageal Cancer

项目总结 本申请是根据PA-18-842号公告提交的。而食道 腺癌(EAC)是美国食道癌的主要细胞类型 鳞状细胞癌(ESCC)在全球范围内发病率明显较高，全球癌症健康状况也较好 负担。在美国，非裔美国人患EAC的几率很低，但受 食管鳞癌的发病风险增加了2-3倍。理解两者之间的关系是至关重要的。 种族与EAC和ESCC风险，因此可以制定针对人群的策略来降低食道 癌症死亡率。由于ESCC在美国的发病率很低，解决这一种族问题极具挑战性 通过对美国人口的研究得出的差异。我们建议研究口腔微生物组作为ESCC的生物标志物。 在发病率较高的南非黑人中，并将利用这些信息深入了解 影响非裔美国人食管鳞癌风险的因素。我们的团队与一家 进行约翰内斯堡癌症研究的南非组织，此前已招募了1,000多人 患有ESCC的南非黑人。我们建议对从这一人群中收集的样本和数据进行试点研究， 结合来自母公司R01的数据，为了深入了解ESCC在美国的种族差异，我们 将对50名患有ESCC的南非黑人和100名匹配的对照组的唾液微生物组进行分析 使用来自亲代R01的EAC和非EAC患者唾液样本来解决以下具体目标：AIM 1：深入了解口腔微生物组作为非裔美国人ESCC风险生物标志物的情况；Subaim 1a： 确定种族差异是否影响EAC的口腔微生物组特征；目标2：确定 食管鳞癌和食管鳞癌患者的口腔微生物群是否存在差异。结果将有助于确定 是否需要不同的口腔微生物组特征来确定非洲裔美国人患EAC的风险，以及 将加强我们对口腔微生物群作为生物标志物和潜在的肿瘤促进剂的理解 对于EAC和ESCC。口腔微生物组可以代表一种简单的非侵入性测试来识别患者 ESCC的高风险，将对非裔美国人有很大好处，并可能有助于缩小 这种高致命性疾病的发病率和结果。

PROJECT SUMMARY This application is being submitted in response to the announcement PA-18-842. While esophageal adenocarcinoma (EAC) is the predominant cell type for esophageal cancer in the United States, esophageal squamous cell cancer (ESCC) has a markedly higher incidence worldwide and greater global cancer health burden. In the U.S. African-Americans have a very low incidence of EAC but are disproportionately affected by ESCC, with a 2-3-fold increased risk of this malignancy. It is critical to understand the relationship between race and EAC and ESCC risk, so that population-tailored strategies can be developed to lower esophageal cancer mortality. Due to the low incidence of ESCC in the U.S., it is extremely challenging to address this racial disparity via studies in U.S. populations. We propose to study the oral microbiome as a biomarker for ESCC among black South Africans, where the incidence is high, and will use this information to gain insights into factors impacting ESCC risk among African-Americans. Our group has an established collaboration with a South African group that carried out the Johannesburg Cancer Study and has previously enrolled over 1,000 black South Africans with ESCC. We propose a pilot study of samples and data collected from this population, combined with those from the parent R01, in order to gain insights into ESCC racial disparities in the U.S. We will profile the salivary microbiome of 50 black South Africans with ESCC and 100 matched controls together with EAC and non-EAC patient saliva samples from the parent R01 to address the following specific aims: Aim 1: To gain insight into the oral microbiome as biomarker for ESCC risk among African-Americans; Subaim 1a: To determine whether racial differences impact an oral microbiome signature for EAC; Aim 2: To determine whether there are differences in the oral microbiome in ESCC and EAC. The results will help determine whether distinct oral microbiome signatures may be needed to identify African-Americans at risk for EAC, and will enhance our understanding of the oral microbiome as both a biomarker and potential neoplastic promoter for EAC and for ESCC. The oral microbiome could represent a simple non-invasive test to identify patients at high risk for ESCC and would be of great benefit to African-Americans and could help reduce disparities in incidence and outcomes of this highly lethal disease.