Safer Approaches to CRC Chemoprevention

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Abstract/Summary Administrative Supplement toR01 CA213987 “Safer approaches to CRC Chemoprevention” Understanding genomic and metabolomic risk factors of CRC in American Indians Vs Caucasians of Oklahoma. This application responds to the PA-18-842 “Administrative Supplements to Support Cancer Disparity Collaborative Research”, and is focused on colorectal cancer (CRC). The long- term goal is to improve community and clinical CRC-related practice for American Indians (AIs) and African Americans (AAs) compared to that of Caucasians (mainly non-Hispanic whites) in Oklahoma. CRC is the second most common cause of cancer-related deaths in both Oklahomans and the US population as a whole. In general, Oklahomans have higher incidence and mortality for most cancers – this is particularly so for CRC where deaths are >21% greater than the US average CRC death rate. It is particularly concerning that Oklahoman AIs have a staggering 63% greater incidence rates >51% higher mortality rates for CRC than the national rate drawn mostly from Caucasian populations. Oklahoman AAs also have higher incidence (~20%) and mortality (54.9%) compared to overall US mortality rates. At present no in-depth studies have been performed to understand the risk factors that contribute to these CRC incidence and mortality rates in Oklahoma’s AIs and AAs compared to Caucasians. Thus, this collaborative administrative supplement focuses on understanding the genomic and metabolomic risk factors with specific focus on the inflammation in CRC patients of AI, AA and Caucasian descent. Our collaborative team includes laboratory based basic researchers (C.V. Rao, Ph.D; H. Yamada, Ph.D, K. Morris, M.D, C. Xu, Ph.D,) and cancer disparities researchers M. Doescher, M.D, from the Stephenson Cancer Center and Upender Manne, Ph.D, (University of Alabama, at Birmingham) the latter with expertise in AA cancer disparities. Our specific goals in this administrative supplement are to establish whether: i) enhanced genomic mutational burden; ii) altered gene expression; and iii) higher systemic and colonic inflammation are key factors contributing to the higher incidence and mortality of Oklahoman AIs and AAs as compared to Oklahoma Caucasian populations. The outcomes will provide a basis to develop novel anti- inflammatory (R01 213987 specific objective) and immune targeted approaches as adjuvants to improve disease free survival in AI and AA CRC patients.