Liver Cancer Disparities in Alaska Native and American Indian People

摘要：AI/AN中肝癌的总体构成差异 肝细胞癌是美国上升最快的主要恶性肿瘤。而与肺、乳腺癌、前列腺癌相关的死亡 而结直肠癌在1990至2016年间大幅下降了40%-53%，肝癌是唯一的主要 男性和女性的死亡率都在上升的恶性肿瘤，其年平均死亡率最高 百分比变化2。肝细胞癌目前是美国第六大癌症相关死亡原因。 到2030年，超过乳腺癌和结直肠癌，成为癌症相关死亡的第三大原因。 美国印第安人/阿拉斯加原住民(AI/AN)面临着不成比例的高肝癌负担。艾/安人有 肝癌发病率是白人的2.4倍，肝癌相关死亡率是白人的2.5倍。艾/安人 有很高的发病率和导致肝细胞癌的情况，如丙型和乙型病毒性肝炎，酒精 使用障碍、NAFLD/NASH、肥胖和糖尿病。此外，AI/AN患者有独特的风险因素和 肝癌发生的致病机制，如乙肝病毒F1B基因型感染的高流行率， 乙肝病毒F1B基因核心区的独特突变与空气污染物(颗粒物)的高暴露 &lt；2.5微米或“PM2.5”)，它们是公认的致癌物。 我们的AI/AN差异中的肝癌(LI-CAD)P20计划的主要焦点是消除 及早发现。我们认为，肝细胞癌管理中最严重的差距和不足，以及 改善的最大机会在于及早发现。该P20计划的总体目标是 将新的、创新的、可转化的方法应用于肝细胞癌的监测和早期发现 通过AI/AN人群中肝癌病理生理学和流行病学的独特方面来消除差异， 改善早期发现，并最终降低与肝癌相关的死亡率。总体战略是引入 基于肝细胞癌风险分层和风险监测的“精准肝细胞癌筛查” P20 LI-CAD计划将实现以下目标： 1.项目1.转变基于生物标记物的监测以早期发现中低危肝癌 AI/AN患者。我们将在AI/AN患者身上测试和调整令人兴奋的生物标志物面板，并开发创新的 纵向(贝叶斯)生物标记物建模策略，以最大化生物标记物的性能特征- 以监视为基础。 2.项目2.开发新的风险分层策略并测试基于MRI的简化早期监测 高危AI/AN患者肝细胞癌的检测。我们将阐明HBV型特异性突变在 为肝癌风险分层和基于风险的监测开发专门针对AI/AN的“肝癌风险计算器”；以及 使用这些肝癌风险计算器识别高危患者，以便采取更密集的肝癌监测策略 利用新的简化磁共振成像方案，将在小规模试点和可行性随机对照试验中进行测试

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