Translational Research Program in Colorectal Cancer Disparities

PROJECT SUMMARY/ABSTRACT – Overall Racial and ethnic disparities in colorectal cancer (CRC) are particularly pronounced in African American and Alaska Native people. These differences cannot be explained by access to screening and health care alone, suggesting underlying yet understudied contributors to disease etiology, progression, and response to treatment.

Ongoing innovations in biotechnology that enable detailed evaluations of the underpinnings of tumor and host molecular genetics and genomic biology have been inadequately leveraged to address these disparities. Collectively, our outstanding transdisciplinary team has the expertise to use cutting-edge technologies to drive

innovative translational cancer disparities research directly focused on developing novel prevention, early detection, diagnosis, and treatment approaches. To achieve our overarching goal of reducing persistent CRC disparities, particularly those present among Alaska Native and African American people, we propose the

following specific aims: Aim 1: Improve risk stratified screening and early detection of CRC across racial and ethnic populations by developing risk prediction models that perform equally well across racial and ethnic groups. Aim 2: Reduce racial and ethnic disparities in CRC-specific mortality by discovering and validating

novel molecular and biological changes related to risk of lethal CRC and response to treatment in racially and ethnically diverse patients that can guide surveillance and treatment selection for CRC survivors. Aim 3: Discover novel therapeutic targets for CRC across racially and ethnically diverse populations and test

potential clinical interventions aimed at reducing CRC disparities by advancing our understanding of differences and similarities in the genetic, molecular, and microbial characteristics of CRC in diverse populations and testing the effectiveness of novel interventions in clinical trials that enroll diverse CRC patients. Our world-

class investigator team has expertise in basic science, clinical and translational research, minority health, and cancer disparities. During the P20 SPORE planning phase we have brought together a large biorepository of various biospecimen types and detailed clinical data from a large, racially and ethnically diverse CRC patient

population with equal numbers of African American, Alaska Native, Hispanic and non-Hispanic White patients, and through our long-term leadership in genetic epidemiology we have access to the world's largest and most racially and ethnically diverse CRC germline genetic data set. Utilizing these unique resources, our program will

conduct four translational projects supported by three essential cores that will provide centralized expertise in: a) leadership and administration, b) biospecimens, pathology and molecular technologies, and c) biostatistics and bioinformatics. Our Career Enhancement and Developmental Research Programs will ensure that we recruit

talented and diverse investigators and develop a pipeline of novel translational cancer disparities research projects. Through this integrated effort we envision realizing our goal of a sustained translational research program focused on eliminating CRC disparities and more broadly reducing CRC-related morbidity and mortality.