Safer Approaches to CRC Chemoprevention

摘要/概要 R 01 CA 213987“更安全的CRC化学预防方法”的行政补充 了解美国印第安人与高加索人中CRC的基因组学和代谢组学风险因素 来自俄克拉荷马州。 本申请响应PA-18-842“支持癌症差异的行政补充” 合作研究”，并专注于结直肠癌（CRC）。我们的长期目标是 美国印第安人（AI）和非洲裔美国人（AA）的社区和临床CRC相关实践 与俄克拉荷马州的高加索人（主要是非西班牙裔白人）相比。CRC是第二大 这是俄克拉荷马州和整个美国人口中癌症相关死亡的常见原因。在 一般来说，俄克拉荷马州的大多数癌症的发病率和死亡率都较高，尤其是 CRC，死亡率比美国平均CRC死亡率高21%。尤其令人关切的是， 俄克拉荷马州的AI有一个惊人的63%以上的发病率>51%的死亡率高CRC 而全国的死亡率主要来自高加索人群。俄克拉荷马州的AA也有更高的 发生率（~20%）和死亡率（54.9%）与美国总体死亡率相比。目前没有深入的 已经进行了研究以了解导致这些CRC发病率的风险因素， 俄克拉荷马州的AI和AAs与白人的死亡率比较。因此，这种合作 行政补充侧重于了解基因组和代谢组学风险因素， 特别关注AI、AA和高加索血统的CRC患者的炎症。我们的协作 团队包括基于实验室的基础研究人员（C. V. Rao，Ph.D; H. Yamada，Ph.D，K. Morris，M.D，C. 和癌症差异研究人员M。Doescher，医学博士，来自斯蒂芬森癌症中心 和Upender Manne博士（位于伯明翰的亚拉巴马大学），后者具有AA癌症的专业知识 差距。我们在本行政补充文件中的具体目标是确定：i）加强 基因组突变负担; ii）改变的基因表达;和iii）更高的全身和结肠炎症 是导致俄克拉荷马州AI和AA的发病率和死亡率较高的关键因素， 到俄克拉荷马州的高加索人。研究结果将为开发新型抗- 炎性（R 01 213987特异性目标）和免疫靶向方法作为佐剂来改善 AI和AA CRC患者的无病生存率。

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.