Liver Cancer Disparities in Alaska Native and American Indian People

阿拉斯加原住民和美洲印第安人的肝癌差异

• 批准号: 10286757
• 负责人: William Mallory Grady
• 金额: $ 101.15万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-06 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10286757
• 关键词: Air Pollutants; Alaska Native; American Indians; Biological Markers; Biometry; Biostatistics Core; Cancer Biology; Cancer Etiology; Carcinogens; Cessation of life; Chad; Characteristics; Chemoprevention; Cherokee Indian; Cirrhosis; Clinical; Clinical Research; Collaborations; Colorectal Cancer; Continuity of Patient Care; Development; Diabetes Mellitus; Early Diagnosis; Effectiveness; Epidemiology; Epigenetic Process; Exposure to; Face; Functional disorder; Genetic; HBV Genotype; Health Services; Health system; Hepatitis B; Hepatitis C; Hepatology; High Prevalence; Incidence; International; Liver; Liver diseases; Longitudinal cohort; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of lung; Malignant neoplasm of prostate; Modeling; Mutation; Native-Born; Obesity; Outcome; Particulate Matter; Pathology; Patients; Performance; Persons; Prevalence; Primary carcinoma of the liver cells; Prognosis; Protocols documentation; Radiology Specialty; Recurrence; Research; Risk; Risk Factors; Role; Testing; Time; United States; Viral hepatitis; Woman; alcohol use disorder; base; biobank; biomarker development; biomarker panel; cancer genetics; cancer health disparity; chronic liver disease; data repository; disparity elimination; fine particles; high risk; improved; innovation; malignant breast neoplasm; men; mortality; multidisciplinary; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; novel marker; programs; prospective; risk stratification; screening; surveillance strategy; translational approach; treatment response; tribal health

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

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。而死亡与肺、乳腺、前列腺有关 1990 年至 2016 年间，结直肠癌急剧下降 40-53%，HCC 是唯一的主要癌症 男性和女性死亡率均呈上升趋势且年平均死亡率最高的恶性肿瘤 百分比变化2。 HCC 目前是美国癌症相关死亡的第六大原因。预计 到2030年，癌症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。 美洲印第安人/阿拉斯加原住民 (AI/AN) 面临着不成比例的高肝癌负担。 AI/AN 人有 与白人相比，HCC 发病率高 2.4 倍，HCC 相关死亡率高 2.5 倍。人工智能/人工智能人 导致 HCC 的疾病的发病率和患病率非常高，例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 患者具有独特的危险因素 HCC 发展的发病机制，例如 F1b 基因型 HBV 感染的高患病率， HBV 基因型 F1b 核心区域的独特突变以及空气污染物（颗粒物）的高暴露 <2.5μm 或“PM2.5”），这是公认的致癌物质。 我们的肝癌 AI/AN 差异 (Li-CAD) P20 计划的主要重点是消除 早期发现。我们认为 HCC 管理中最关键的差异和缺陷，以及 最大的改进机会在于早期发现。 P20 计划的总体目标是 应用新颖、创新、转化的方法来监测和早期发现 HCC 通过 AI/AN 人群 HCC 病理生理学和流行病学的独特方面，以消除差异， 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HCC风险分层和风险监测的“精准HCC筛查” P20 Li-CAD 计划将实现以下目标： 1. 项目 1. 转变基于生物标志物的监测，以早期发现中低风险的 HCC 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组，并开发创新的 纵向（贝叶斯）生物标志物建模策略，以最大化生物标志物的性能特征 为基础的监视。 2. 项目 2. 制定新的风险分层策略并测试基于 MRI 的早期监测 高危 AI/AN 患者中 HCC 的检测。我们将阐明 HBV 基因型特异性突变在 肝癌；开发 AI/AN 专用的“HCC 风险计算器”，用于 HCC 风险分层和基于风险的监测；和 使用这些 HCC 风险计算器来识别高风险患者，以实施更强化的 HCC 监测策略 利用新颖的简化 MRI 协议，该协议将在小型试点和可行性 RCT 中进行测试