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 mg β-胡萝卜素和25，000 IU 棕榈酸视黄酯在18，314名肺癌高危人群中的应用该试验于1985年开始招募， 1996年1月停止，比计划提前21个月，得出两个结论：没有好处， 有证据表明，干预措施对肺癌发病率和总死亡率都有有害影响。参与者 干预后继续随访9年以上，更新肺癌发病率， 2004年发表的心血管疾病死亡率调查结果。2005年6月30日，CARET停止积极跟进- 的参与者。在CARET的主动干预阶段，血清、血浆、全血（用于DNA）和 收集肺组织标本。这些生物标本组成了CARET生物储存库， 这个应用程序的重点。CARET生物储存库是研究疾病发展的关键工具， 进展这是母试验的宝贵遗产，任何研究者都可以获得样本， 假设驱动项目。 当前赠款周期（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 值;以及肺癌、前列腺癌、结肠癌和乳腺癌病例诊断时的分期。我们还扩展了CARET 2012/13年度，通过与国家死亡率监测中心的联系，对癌症诊断、死亡和死亡原因进行跟踪 索引，康涅狄格州癌症登记处，以及加州和华盛顿癌症登记处。这 大大增加了确定的癌症病例总数（n= 6，773），并扩大了 整个队列的随访（首次诊断的中位随访时间为18年，死亡为20年）。在我们 目标是在当前的赠款周期（2013 - 2018年）内，使CARET生物储存库能够获得生物标本， 和/或数据已提供给研究人员，这导致了23个同行评审的出版物。 目前有93个正在进行的项目利用CARET生物标本。 在这项申请中，我们要求资金继续支持CARET生物储存库和相关的 广泛的数据库。我们亦建议试行有关程序，以取得经签署的最新医疗纪录 并同意在CARET生物储存库中使用生物材料， 为广泛的研究目的和数据共享获得同意方面的进展。此外，为了定位 CARET用于检查肿瘤异质性和分子亚型与病因学之间关系的研究 因素和生存率，我们建议进行试点，以获得诊断肺癌活检/手术标本 来自2003年后确诊的华盛顿州CARET参与者。这将包括获得更新的版本 医疗记录和同意广泛的研究目的和数据共享。

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.