Infrastructure Support and Pilot Tissue Collection for the CARET Biorepository

CARET 生物样本库的基础设施支持和试点组织采集

• 批准号: 10374863
• 负责人: Marian L Neuhouser
• 金额: $ 59.53万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374863
• 关键词: All-Trans-Retinol; Asbestos; Award; Beta Carotene; Biocompatible Materials; Biological; Biological Markers; Biological Specimen Banks; Biological Specimen database; Biopsy; California; Cancer Prevention Trial; Cardiovascular Diseases; Carotene; Cause of Death; Cessation of life; Characteristics; Cigarette Smoker; Clinical; Clinical Data; Collection; Colon Carcinoma; Connecticut; Consent; DNA; Data; Databases; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Early Diagnosis; Endpoint Determination; Enrollment; Etiology; Exposure to; Funding; Funding Mechanisms; Goals; Government; Grant; Human Resources; Incidence; Infrastructure; Intervention; Intervention Trial; Investigation; Laboratories; Life Style; Maintenance; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Malignant neoplasm of urinary bladder; Medical Records; Micronutrients; Minerals; Molecular Epidemiology; Occupational Exposure; Operative Surgical Procedures; Parents; Participant; Peer Review; Persons; Phase; Plasma; Population; Populations at Risk; Positioning Attribute; Prevention; Procedures; Prognosis; Publications; Publishing; Randomized; Records; Research; Research Personnel; Resected; Resources; Safety; Sampling; Schedule; Serum; Site; Smoking History; Specimen; Stage at Diagnosis; Structure of parenchyma of lung; Time; Tissue Banks; Tissue Sample; Tissues; Tobacco; Tumor Tissue; Twin Multiple Birth; United States National Institutes of Health; Update; Vitamins; Washington; Whole Blood; Woman; biobank; cancer diagnosis; cancer epidemiology; cancer prevention; cigarette smoking; cohort; cost; data sharing; dietary; double-blind placebo controlled trial; early detection biomarkers; editorial; efficacy trial; follow-up; genetic analysis; genetic epidemiology; high risk; high risk population; improved; indexing; intervention effect; malignant breast neoplasm; men; molecular subtypes; mortality; neoplasm registry; nutrition; nutritional epidemiology; personalized medicine; post intervention; public database; recruit; repository; research and development; retinyl palmitate; tobacco abuse; tool; tumor; tumor heterogeneity; web site

Project Summary The Carotene and Retinol Efficacy Trial (CARET) was a randomized, double-blind, placebo-controlled trial of the cancer prevention efficacy and safety of a daily combination of 30 mg of β-carotene and 25,000 IU of retinyl palmitate in 18,314 persons at high risk for lung cancer. The trial began recruitment in 1985 and was halted in January 1996, 21 months ahead of schedule, with the twin conclusions of no benefit and substantial evidence of a harmful effect of the intervention on both lung cancer incidence and total mortality. Participants continued to be followed for over nine years post-intervention, with updated lung cancer incidence and cardiovascular disease mortality findings published in 2004. On June 30, 2005, CARET stopped active follow- up of participants. During the active intervention phase of CARET, serum, plasma, whole blood (for DNA), and lung tissue specimens were collected. These biospecimens make up the CARET biorepository, which is the focus of this application. The CARET biorepository is a key tool in studying disease development and progression. It is an invaluable legacy of the parent trial with specimens available to any investigator with a hypothesis-driven project. The specific aims of the current grant cycle (2013-2018) included extending the database and online accessibility to include participant use of micronutrient, mineral, and vitamin supplements; baseline laboratory values; and stage at diagnosis of lung, prostate, colon, and breast cancer cases. We also extended CARET follow-up of cancer diagnoses, deaths, and causes of death through 2012/13 via linkages to the National Death Index, Cancer Registry of Connecticut, and the Cancer Registries of California and Washington. This has greatly increased the total numbers of identified incident cancer cases (n=6,773) as well as extending the follow-up of the entire cohort (median follow-up to first diagnosis is 18 years and to death is 20 years). In our goal to make the CARET biorepository accessible, during the current grant cycle (2013 – 2018), biospecimens and /or data have been provided to investigators, which have resulted in 23 peer-reviewed publications. Currently there are 93 ongoing projects utilizing CARET biospecimens. In this application, we request funds to continue support of the CARET biorepository and the associated extensive database. We also propose to pilot procedures to obtain updated signed releases of medical records and consent for the utilization of biologic material in the CARET biorepositories consistent with recent developments on obtaining consent for broad research purposes and data sharing. In addition, to position CARET for studies examining the association of tumor heterogeneity and molecular subtypes with etiologic factors and survival, we propose to conduct a pilot to obtain diagnostic lung cancer biopsy/surgical specimens from Washington State CARET participants diagnosed after 2003. This will include obtaining updated release of medical records and consent for broad research purposes and data sharing.

项目概要 胡萝卜素和视黄醇功效试验 (CARET) 是一项随机、双盲、安慰剂对照试验， 每日服用 30 毫克 β-胡萝卜素和 25,000 IU 胡萝卜素组合的癌症预防功效和安全性 棕榈酸视黄酯用于 18,314 名肺癌高危人群。该试验于 1985 年开始招募， 1996年1月停止，比计划提前了21个月，得出了“没有好处”和“实质性好处”的双重结论。 有证据表明干预措施对肺癌发病率和总死亡率产生有害影响。参加者 干预后继续跟踪九年多，更新肺癌发病率和 2004 年发表的心血管疾病死亡率调查结果。2005 年 6 月 30 日，CARET 停止了积极的随访 的参与者。在 CARET 的主动干预阶段，血清、血浆、全血（DNA）和 采集肺组织标本。这些生物样本组成了 CARET 生物样本库， 本应用的重点。 CARET 生物样本库是研究疾病发生和发展的关键工具 进展。这是母体试验的宝贵遗产，任何具有相关研究能力的研究者都可以获得样本。 假设驱动的项目。 当前资助周期（2013-2018）的具体目标包括扩展数据库和在线 参与者使用微量营养素、矿物质和维生素补充剂的可及性；基线实验室 价值观；肺癌、前列腺癌、结肠癌和乳腺癌病例的诊断阶段。我们还扩展了 CARET 通过与全国死亡信息的联系，对 2012/2013 年癌症诊断、死亡和死亡原因进行跟踪 索引、康涅狄格州癌症登记处以及加利福尼亚州和华盛顿州癌症登记处。这有 大大增加了已发现的癌症病例总数（n = 6,773），并延长了 对整个队列进行随访（首次诊断的中位随访时间为 18 年，至死亡的中位随访时间为 20 年）。在我们的 目标是在当前拨款周期（2013 - 2018）内使 CARET 生物样本库可访问，生物样本 和/或数据已提供给研究人员，从而发表了 23 篇经过同行评审的出版物。 目前有 93 个正在进行的项目利用 CARET 生物样本。 在此申请中，我们请求资金来继续支持 CARET 生物存储库和相关的 广泛的数据库。我们还建议试点程序以获得更新的签名医疗记录版本 并同意在 CARET 生物储存库中使用生物材料，与最近的一致 为广泛研究目的和数据共享获得同意的进展。另外，要定位 CARET 用于检查肿瘤异质性和分子亚型与病因之间的关联的研究 因素和生存率，我们建议进行试点以获得诊断性肺癌活检/手术标本 来自 2003 年之后诊断的华盛顿州 CARET 参与者。这将包括获取更新版本 用于广泛研究目的和数据共享的医疗记录和同意书。