Project 2: Mitigating Lung Cancer Disparities in Native Hawaiians: A Population-Based Approach to Evaluate Prevention Barriers and Lung Tumor Biology

项目 2：减少夏威夷原住民的肺癌差异：基于人群的方法来评估预防障碍和肺癌生物学

• 批准号: 10716155
• 负责人: Sungshim Lani Park
• 金额: $ 29.46万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10716155
• 关键词: Accounting; Address; Adenocarcinoma; Adenocarcinoma Cell; Adherence; Adult; African American population; Age; Archives; Behavior; Belief; Biological; Biological Factors; Biological Markers; Biological Process; Cancer Burden; Cancer Intervention and Surveillance Modeling Network; Cancer Patient; Carcinogens; Characteristics; Chest; Cigarette; Cohort Studies; Collaborations; Communities; DNA; DNA Methylation; DNA Sequence Analysis; Data; Data Set; Development; Diagnosis; Disease; Disease Outcome; Disparity; Dose; Early Diagnosis; Eligibility Determination; Epigenetic Process; Ethnic Population; European; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic study; Grant; Guidelines; Hawaii; Hawaiian population; Health; Health behavior; Health education; Healthcare; Heterogeneity; Histologic; Immune; Individual; Intervention; Interview; Japanese American; Knowledge; Leukocytes; Lung; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Medical; Metabolism; Methylation; Michigan; Minority Groups; Modality; Modeling; Molecular; Molecular Analysis; Molecular Profiling; Mutation; Native Hawaiian; Nicotine; Not Hispanic or Latino; Participant; Patients; Pattern; Perception; Performance; Population; Population Sciences; Prevention; Prognostic Factor; Provider; Recommendation; Risk; Role; Scanning; Smoke; Smoker; Smoking; Smoking Behavior; Smoking History; Squamous cell carcinoma; Tobacco-Associated Carcinogen; Translating; Treatment Efficacy; Tumor Biology; Tumor Tissue; Tumorigenicity; Underserved Population; United States Preventative Services Task Force; Universities; aged; burden of illness; cancer diagnosis; cancer health disparity; cancer risk; cell type; cohort; computed tomography screening; design; ethnic difference; ethnic minority; experience; follow-up; genome-wide; high risk; improved; informant; low dose computed tomography; lung cancer screening; minority health disparity; mortality; multi-ethnic; population based; predictive modeling; racial difference; racial minority; racial population; risk prediction model; screening; screening guidelines; small cell lung carcinoma; smoking cessation; targeted treatment; translational study; treatment strategy; tumor; tumor microenvironment; tumor-immune system interactions; underserved minority; uptake

ABSTRACT We have shown in the Multiethnic Cohort (MEC) that Native Hawaiians have a markedly higher risk of lung cancer and a poorer survival from the disease compared to (non-Hispanic) Whites, even after accounting for smoking history and other risk/prognostic factors. This excess risk was observed for the two most common histologic cell-types: adenocarcinoma and squamous cell carcinoma as well as for small-cell lung cancer, a more aggressive cell-type. The poorer survival is observed with early stage and not advanced disease. We have made extensive efforts in the study of genetics, epigenetics and smoking and tobacco carcinogens-related biomarkers to understand the differences in lung cancer risk across populations. While the high risk in African Americans and low risk in Japanese Americans can be explained by higher and lower smoking intensity (carcinogens dose per cigarette), due to smoking behavior and lower nicotine metabolism, respectively, reasons for the risk excess in Native Hawaiians remain to be elucidated. Lung cancer screening using low-dose Computed Tomography (LDCT) among adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke, or have quit within the past 15 years, has been found to decrease mortality. However, the state of Hawaii ranks last in the proportion of lung cancers diagnosed at an early stage (19% vs. the national average of 24%), with less than 3% of high-risk smokers undergoing LDCT scan (national average is 6%). Studies have suggested that the use of risk-based prediction models may be more effective than the U.S. Preventive Services Task Force (USPSTF) criteria at identifying high-risk smokers for lung cancer screening. However, both the USPSTF guidelines and these risk prediction models were derived from data collected in mostly European-descent populations. We also found that there may be distinct biological processes related to tumorigenicity that contribute to the excess risk and poor disease outcomes for Native Hawaiians. We observed differences in epigenetic patterns in blood leukocyte DNA associated with smoking dose in Native Hawaiians when compared to other racial/ethnic groups, with the differential methylation occurring in cancer-related genes. To reduce the lung cancer burden of Native Hawaiians, we propose a multilevel translational study to identify the individual- and provider-based barriers for lung cancer screening to develop an intervention strategy to be disseminated in collaboration with the Hawaii Department of Health (Aim 1), to better identify those at greatest risk of developing lung cancer by computing a Native Hawaiian-specific risk prediction model (Aim 2), and to characterize the tumor pathobiology associated with the poor survival of Native Hawaiian lung cancer patients (Aim 3). Study findings will provide critical information along the continuum of lung cancer healthcare for a high risk minority population. During this grant cycle, we will develop collaborations to translate our findings into validated culturally-tailored, precision-based interventions to increase early detection and efficacy of treatment modalities in this high-risk underserved minority population.

抽象的 我们在多种族队列 (MEC) 中表明，夏威夷原住民患肺癌的风险明显更高 与（非西班牙裔）白人相比，即使考虑到癌症，该疾病的生存率也较差 吸烟史和其他风险/预后因素。在两种最常见的情况下观察到这种超额风险 组织学细胞类型：腺癌和鳞状细胞癌以及小细胞肺癌，更多 攻击性细胞类型。早期疾病而非晚期疾病的生存率较差。我们已经做了 在遗传学、表观遗传学以及吸烟和烟草致癌物相关生物标志物的研究方面做出了广泛的努力 了解不同人群肺癌风险的差异。虽然非裔美国人的风险很高 日裔美国人的低风险可以通过较高和较低的吸烟强度来解释（致癌物剂量） 每支烟），分别由于吸烟行为和较低的尼古丁代谢，导致风险过高的原因 夏威夷原住民的情况仍有待阐明。使用低剂量计算机断层扫描进行肺癌筛查 (LDCT) 年龄在 50 至 80 岁、有 20 包年吸烟史且目前吸烟的成年人，或 研究发现，过去 15 年内戒烟可以降低死亡率。然而夏威夷州排名垫底 早期诊断出肺癌的比例（19%，全国平均水平为 24%）， 超过 3% 的高危吸烟者接受 LDCT 扫描（全国平均水平为 6%）。研究表明， 使用基于风险的预测模型可能比美国预防服务工作组更有效 (USPSTF) 确定高危吸烟者进行肺癌筛查的标准。然而，USPSTF 指南和这些风险预测模型来自于大多数欧洲血统收集的数据 人口。我们还发现可能存在与致瘤性相关的独特生物过程 导致夏威夷原住民面临过高的风险和不良的疾病结果。我们观察到差异 夏威夷原住民血液白细胞 DNA 中与吸烟剂量相关的表观遗传模式进行比较 与其他种族/族裔群体相比，癌症相关基因中存在差异甲基化。为了减少 夏威夷原住民的肺癌负担，我们提出了一项多层次转化研究来确定个体- 和基于提供者的肺癌筛查障碍，以制定干预策略并在以下地区传播 与夏威夷卫生部合作（目标 1），以更好地识别那些面临最大风险的人群 通过计算夏威夷原住民特定的风险预测模型（目标 2）来诊断肺癌，并表征肿瘤 与夏威夷原住民肺癌患者生存率低相关的病理生物学（目标 3）。研究结果 将为高危少数群体提供肺癌医疗保健连续性的关键信息。 在此资助周期中，我们将开展合作，将我们的发现转化为经过验证的、适合文化的、 基于精确的干预措施，以提高这一高风险人群的早期发现和治疗方式的有效性 服务不足的少数民族人口。