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

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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.