Hawaii Minority Health and Cancer Disparities SPORE

项目总结/摘要 健康差距的根源在于生物、行为、社会文化和 个体和群体的环境特征。夏威夷为少数民族提供了特殊的机会 健康研究，因为其独特的多样性人口与不同的癌症负担和高质量的健康 护理和癌症登记。夏威夷大学癌症中心有一个成功的记录， 夏威夷的多种族人口研究种族/种族差异在癌症风险和结果。搭建了一个 面向社区的基础设施，将这些发现转化为重大的生物学发现和临床 这些创新将有助于缓解美国的癌症差异。我们在本P50（PAR-20-305）中建议， 建立一个SPORE计划，以进行翻译研究，重点是亚裔美国人，夏威夷土著人 和太平洋岛民（AANHPI），增长最快的美国少数民族，最初解决三种癌症，特别是 高度相关性。项目1将通过以下方式解决该人群中肝细胞癌（HCC）的高发病率问题： 在患有非酒精性脂肪肝（NAFLD）的AANHPI患者中实施随机生活方式干预 通过研究机制生物标志物（无细胞和白细胞DNA甲基化），也可以提供 急需的临床管理工具。我们将测试间歇性与持续性能量限制的有效性 逆转AANHPI中NAFLD的进展，AANHPI是慢性肝病和肝脏疾病的最常见病因， 癌症在这个人群中。项目2将解决夏威夷原住民经历的过度肺癌负担 通过开发一种基于风险和文化信息的肺癌筛查策略，并研究突变， 肺鳞状细胞癌、小细胞癌和腺癌的甲基化和转录组学特征 这导致了这一弱势群体无法解释的贫困生存。项目3将解决非常高的 夏威夷原住民的乳腺癌负担和亚裔美国人的乳腺癌发病率上升， 目前用于预测这些人群中乳腺癌的放射组学风险预测算法， 乳腺肿瘤环境的相关分子和组织病理学特征，可能与内脏 肥胖并具有预后意义。我们还将建立：1）一个具有战略意义的行政核心 规划、咨询和评估部分; 2）外展和招聘核心（ORC）促进 少数民族的研究; 3）配对新鲜冷冻肿瘤和血液样本的集中生物储存库，以及 作为存档肿瘤块（病理学和生物标本核心）; 4）生物统计学和生物信息学核心; 5）a 发展研究计划，以资助创新的试点研究和职业提升计划， 支持有前途的研究人员新的转化研究;和6）新的合作，与其他机构 进一步翻译我们的发现这项赠款的成功完成将大大推动我们的 有能力降低AANHPI中肝癌、肺癌和乳腺癌的高负担，并进行其他创新 转化少数民族健康研究，将有利于夏威夷，太平洋地区和美国其他地区。

Project Summary/Abstract At the root of health disparities is the diversity that exists in the biological, behavioral, sociocultural, and environmental characteristics of individuals and populations. Hawai`i offers exceptional opportunities for minority health research due to its uniquely diverse population with varying cancer burdens and its high-quality health care and cancer registration. The University of Hawai`i Cancer Center has a successful track record of leveraging Hawai`i's multiethnic population to study racial/ethnic differences in cancer risk and outcomes. It has built a community-facing infrastructure to translate these findings into major biological discoveries and clinical innovations that would help to alleviate cancer disparities in the US. We propose in this P50 (PAR-20-305) to establish a SPORE program to conduct translational research focusing on Asians Americans, Native Hawaiians and Pacific Islanders (AANHPI), the fastest growing US minority, to initially address three cancers of particularly high relevance. Project 1 will address the high rates of hepatocellular carcinoma (HCC) in this population by implementing a randomized lifestyle intervention among AANHPI patients with non-alcoholic fatty liver (NAFLD) and by investigating mechanistic biomarkers (cell-free and leukocyte DNA methylation) that may also provide much needed clinical management tools. We will test the efficacy of intermittent vs. continuous energy restriction to reverse the progression of NAFLD in AANHPI, the most common etiology of chronic liver disease and liver cancer in this population. Project 2 will address the excess lung cancer burden experienced by Native Hawaiians by developing a risk-based and culturally-informed lung cancer screening strategy, and investigate the mutation, methylation and transcriptomic profiles of lung squamous cell and small cell carcinomas and adenocarcinomas that contribute to the unexplained poor survival in this vulnerable population. Project 3 will address the very high breast cancer burden of Native Hawaiians and the rising rates in Asian Americans by testing the adequacy of current radiomic risk prediction algorithms for predicting breast cancer in these populations and by investigating related molecular and histopathologic features of breast tumor environment which may be related to visceral adiposity and have prognostic significance. We will also establish: 1) an Administrative Core with strategic planning, advisory and evaluation components; 2) an Outreach and Recruitment Core (ORC) facilitating studies among minorities; 3) a centralized biorepository of paired fresh-frozen tumor and blood samples, as well as archival tumor blocks (Pathology & Biospecimen Core); 4) a Biostatistics & Bioinformatics Core; 5) a Developmental Research Program to fund innovative pilot studies and a Career Enhancement Program to support promising investigators new to translational research; and 6) new collaborations, with other institutions for the further translation of our findings. The successful completion of this grant will significantly advance our ability to reduce the high burden of liver, lung and breast cancers in AANHPI and to conduct other innovative translational minority health research that will benefit Hawai`i, the Pacific region and the rest of the US.