Liver Cancer Disparities in Alaska Native and American Indian People

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ABSTRACT: OVERALL COMPONENT - LIVER CANCER DISPARITIES IN AI/AN HCC is the fastest-rising major malignancy in the United States. While deaths related to lung, breast, prostate and colorectal cancer have declined dramatically by 40-53% between 1990 and 2016, HCC is the only major malignancy whose mortality is rising in both men and women and has had the highest average annual percentage change2. HCC is now the 6th leading cause of cancer-related death in the U.S. It is projected to surpass breast and colorectal cancer to become the 3rd leading cause of cancer-related death by 2030. American Indian/Alaska Native (AI/AN) people face a disproportionally high burden of HCC. AI/AN people have 2.4 times higher HCC incidence and 2.5 times higher HCC-related mortality than white persons. AI/AN people have a very high incidence and prevalence of conditions that cause HCC such as viral hepatitis C and B, alcohol use disorders, NAFLD/NASH, obesity and diabetes. Additionally, AI/AN patients have unique risk factors and pathogenetic mechanisms for HCC development, such as high prevalence of infection with HBV genotype F1b, unique mutations in the core region of HBV genotype F1b and high exposure to air pollutants (particulate matter <2.5µm or “PM2.5”), which are recognized carcinogens. The main focus of our Liver Cancer in AI/AN Disparities (Li-CAD) P20 program is to eliminate disparities in EARLY DETECTION. We believe that the most critical disparities and deficiencies in HCC management, and the greatest opportunities for improvement, lie in early detection. The overarching aim of this P20 Program is to apply novel, innovative, translational approaches to surveillance and early detection of HCC that are informed by unique aspects of HCC pathophysiology and epidemiology in AI/AN people in order to eliminate disparities, improve early detection and ultimately reduce HCC-related mortality. The overarching strategy is to introduce “Precision HCC Screening” based on HCC risk stratification and risk-based surveillance The P20 Li-CAD program will achieve the following AIMS: 1. PROJECT 1. Transform biomarker-based surveillance for early detection of HCC in medium and low-risk AI/AN patients. We will test and adapt exciting biomarker panels in AI/AN patients and develop innovative longitudinal (Bayesian) biomarker modeling strategies to maximize the performance characteristics of biomarker- based surveillance. 2. PROJECT 2. Develop novel risk stratification strategies and test abbreviated MRI-based surveillance for early detection of HCC in high-risk AI/AN patients. We will elucidate the role of HBV genotype-specific mutations in HCC; develop AI/AN-specific “HCC Risk Calculators” for HCC risk stratification and risk-based surveillance; and use these HCC Risk Calculators to identify high-risk patients for more intensive HCC surveillance strategies utilizing novel abbreviated MRI protocols, which will be tested in a small pilot and feasibility RCT