Hawaii Minority Health and Cancer Disparities SPORE

项目摘要/摘要 健康差距的根源是存在于生物、行为、社会文化和 个人和群体的环境特征。夏威夷为少数族裔提供了难得的机会 因其独特的多样化人口和不同的癌症负担以及高质量的健康而进行的健康研究 护理和癌症登记。夏威夷大学癌症中心在利用 夏威夷的多民族人口研究癌症风险和结果的种族/民族差异。它已经建立了一个 面向社区的基础设施，将这些发现转化为重大生物学发现和临床 有助于缓解美国癌症差异的创新。我们在本P50(PAR-20-305)中建议 建立一个孢子项目，以亚裔美国人、夏威夷原住民为重点进行翻译研究 和太平洋岛民(AANHPI)，美国增长最快的少数民族，最初解决三种癌症，特别是 关联性很强。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 对AANHPI非酒精性脂肪肝患者实施随机生活方式干预 通过研究机械性生物标记物(无细胞和白细胞DNA甲基化)，也可能提供 急需的临床管理工具。我们将测试间歇性和持续性能源限制的效果。 逆转AANHPI的NAFLD进展，AANHPI是慢性肝病和肝脏最常见的病因 这一人群中的癌症患者。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，并调查突变， 肺鳞状细胞癌、小细胞癌和腺癌的甲基化和转录水平 这导致了这一脆弱群体中无法解释的低存活率。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发病率的上升 目前用于预测这些人群乳腺癌的放射学风险预测算法以及通过调查 乳腺肿瘤环境的相关分子和组织病理学特征可能与内脏有关 肥胖和预后有一定的意义。我们还将建立：1)具有战略意义的行政核心 规划、咨询和评价部分；2)一个外联和征聘核心(ORC)，促进 对少数族裔的研究；3)一对新鲜冷冻的肿瘤和血液样本的中央生物库 作为档案肿瘤块(病理学和生物医学核心)；4)生物统计学和生物信息学核心；5)a 资助创新先导研究的发展研究计划和职业发展计划，以 支持新接触翻译研究的有前途的研究人员；以及6)与其他机构开展新的合作 以便进一步翻译我们的发现。这笔赠款的成功完成将大大推进我们的 有能力减轻AANHPI的高肝癌、肺癌和乳腺癌负担，并进行其他创新 将使夏威夷、太平洋地区和美国其他地区受益的翻译性少数族裔健康研究。

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.