Liver Cancer Disparities in Alaska Native and American Indian People

摘要：总体组成部分-AI/AN中的肝癌差异 HCC是美国增长最快的主要恶性肿瘤。而与肺、乳腺、前列腺有关的死亡 在1990年至2016年期间，肝癌和结直肠癌的发病率急剧下降了40-53%，肝癌是唯一的主要癌症。 男性和女性的死亡率都在上升， 百分比变化2. HCC现在是美国癌症相关死亡的第六大原因。 到2030年，它将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）面临着非常高的HCC负担。AI/AN人有 2.4 HCC的发病率是白色人的1倍，HCC相关死亡率是其2.5倍。AI/AN人物 导致HCC的疾病如丙型和B型病毒性肝炎、酒精 使用障碍、NAFLD/NASH、肥胖和糖尿病。此外，AI/AN患者具有独特的风险因素， HCC发展的发病机制，如HBV基因型F1 b的高感染率， HBV基因型F1 b核心区的独特突变和高度暴露于空气污染物（颗粒物） <2.5µm或“PM2.5”），是公认的致癌物。 我们的AI/AN差异中的肝癌（Li-CAD）P20计划的主要重点是消除AI/AN差异。 早期检测。我们认为，合同委员会管理方面最严重的差距和缺陷， 最大的改进机会在于早期发现。该P20计划的总体目标是 应用新的、创新的、转化的方法来监测和早期发现HCC， 通过AI/AN人群中HCC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HCC相关死亡率。总体战略是引入 基于肝癌风险分层和基于风险的监测的“精确肝癌筛查” P20 Li-CAD计划将实现以下目标： 1.项目1.基于转化生物标志物的监测用于中、低风险HCC的早期检测 AI/AN患者。我们将在AI/AN患者中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）生物标志物建模策略，以最大限度地提高生物标志物的性能特征- 基于监视。 2.项目2.开发新的风险分层策略，并测试基于MRI的早期监测 在高风险AI/AN患者中检测HCC。我们将阐明HBV基因型特异性突变在 HCC;开发AI/AN特定的“HCC风险计算器”，用于HCC风险分层和基于风险的监测;以及 使用这些HCC风险计算器来识别高危患者，以便采取更密集的HCC监测策略 利用新的简化MRI方案，将在小型试点和可行性RCT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