Infrastructure Support and Pilot Tissue Collection for the CARET Biorepository

项目摘要 胡萝卜素和视黄醇疗效试验(CARET)是一项随机、双盲、安慰剂对照试验。 每日30毫克β-胡萝卜素和25,000国际单位联合应用预防癌症的有效性和安全性 18,314名肺癌高危人群中的维生素C棕榈酸酯。审判于1985年开始招募，并于 于1996年1月停止，比原计划提前了21个月，得出了无益和实质性的双重结论 干预措施对肺癌发病率和总死亡率产生有害影响的证据。参与者 干预后继续跟踪超过九年，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停止了活跃的关注- 参赛者人数上升。在CARET的主动干预阶段，血清、血浆、全血(DNA)和 收集肺组织标本。这些生物标本组成了Caret生物资源库，这是 此应用程序的焦点。CARET生物信息库是研究疾病发展和 进步。这是父母试验的宝贵遗产，任何具有 假设驱动的项目。 本赠款周期(2013-2018年)的具体目标包括扩大数据库和在线 可获得性，包括参与者使用微量营养素、矿物质和维生素补充剂；基线实验室 价值；以及肺癌、前列腺癌、结肠癌和乳腺癌的诊断阶段。我们还扩展了Caret 通过与全国死亡的联系，在2012/13年度前跟踪癌症诊断、死亡和死因 指数，康涅狄格州癌症登记处，加利福尼亚州和华盛顿州癌症登记处。这有 大大增加了已查明的癌症病例总数(n=6,773)，并延长了 整个队列的随访(首次诊断的随访中位数为18年，死亡的中位数为20年)。在我们的 目标是在本赠款周期(2013-2018年)期间使CARET生物储存库可供使用，生物检疫 和(或)向调查人员提供了数据，从而产生了23份经同行审查的出版物。 目前有93个正在进行的项目使用CARET生物检疫剂。 在本申请中，我们请求资金继续支持CARET生物存储库和相关的 庞大的数据库。我们还建议试行获取最新签署的医疗记录新闻稿的程序 并同意在CARET生物仓库中使用生物材料，与最近的 在为广泛的研究目的和数据共享获得同意方面的进展。此外，要定位 CARET用于研究肿瘤异质性和分子亚型与病因学的关系 因素和生存率，我们建议进行一项试点，以获得诊断肺癌的活检/手术标本 来自华盛顿州的CARET参与者被诊断为2003年后。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。

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.