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：整体成分 - AI/AN的肝癌差异 HCC是美国升高最快的主要恶性肿瘤。而死亡与肺，乳房，前列腺有关 在1990年至2016年之间，大肠癌和结直肠癌的下降幅度急剧下降了40-53％，HCC是唯一的主要 男性和女性的死亡率正在增加，并且年平均年龄最高 百分比更改2。 HCC现在是美国与癌症相关死亡的第六个主要原因 到2030年，超越乳腺癌和大肠癌成为癌症相关死亡的第三主要原因。 美洲印第安人/阿拉斯加本地人（AI/AN）人面临的HCC燃烧不成比例。人民/一个人有 HCC发病率是2.4倍，与白人相关的HCC相关死亡率高2.5倍。人民/一个人 引起HCC（例如病毒肝炎），酒精的疾病的出现很高的事件和患病率 使用疾病，NAFLD/NASH，肥胖和糖尿病。此外，AI/A A的患者具有独特的危险因素和 HCC发育的致病机制，例如HBV基因型F1B感染的高流行率， HBV基因型F1B的核心区域中的独特突变和空气污染物的高暴露（颗粒物） <2.5µm或“ PM2.5”），是识别的致癌物。 我们肝癌在AI/A/A差异（LI-CAD）P20计划中的主要重点是消除差异 早期检测。我们认为，HCC管理中最关键的分布和缺陷，以及 改进的最大机会，是早期发现。该P20程序的总体目的是 采用新颖，创新的翻译方法来监视和早期发现HCC 通过AI/A/A的HCC病理生理学和流行病学的独特方面，以消除分布， 改善早期检测并最终降低与HCC相关的死亡率。总体策略是介绍 基于HCC风险分层和基于风险的监视的“精度HCC筛查” P20 LI-CAD计划将实现以下目的： 1。项目1。转化基于生物标志物的监视，以早期检测中等和低风险的HCC AI/A A A/A。我们将在AI/A AN患者中测试和适应激动人心的生物标志物面板并发展创新 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 基于监视。 2。项目2。制定新颖的风险分层策略并提早测试基于MRI的缩写 在高风险AI/A A A/A的患者中检测HCC。我们将阐明HBV基因型特异性突变在 HCC;为HCC风险分层和基于风险的监视开发AI/AN特定的“ HCC风险计算器”；和 使用这些HCC风险计算器来识别高风险患者以进行更密集的HCC监视策略 使用新颖的缩写MRI方案，该方案将在小型飞行中进行测试和可行性RCT