Familial Colorectal Neoplasia Collaborative Group

描述(由申请人提供)： 梅奥诊所是合作家庭注册中心(CFR)的创始成员之一，CFR是由NCI支持的六个中心组成的联盟，成立于1997年，旨在建立一个全面的合作基础设施，以促进对结直肠癌(CRC)遗传学和流行病学的跨学科研究。CFR中心使用共同的数据收集协议和核心工具，招募CRC先证者及其亲属。到目前的招募阶段结束时(2002年7月)，儿童基金会将从7 773名先证者、15 232名亲属(受影响和未受影响的)和2000多名无关的对照人员那里获得累积数据和生物检验品，这表明儿童基金会作为一个整体的生产力水平很高。为了充分实现CFR的研究潜力，我们在未来五年集体提出以下具体施舍：(1)集中招募高危家庭和(2)少数族裔(非裔美国人和 (3)对CFR参与者进行系统跟踪；(4)确定DNA错配修复(MMR)基因突变的所有携带者；(5)维护CFR生物谱库；(6)维持生物信息学支持活动；(7)利用CFR基础设施建立新鲜冰冻组织储存库。 经济高效地确定大量高危家庭一直是梅奥CFR设计的一大优势。我们在招募高危家庭和收集肿瘤块方面已经达到并超过了最初的目标。梅奥集团S对整个CFR的承诺从我们领导编写两份竞争性补充材料来证明，这两份补充材料支持登记范围的基本活动(微创肿瘤检测和生物制品加工)，我们的 合作研究活动，以及我们在所有CFR工作组中的积极作用。为了这次更新，梅奥癌症研究中心建议从梅奥诊所罗切斯特招募160名高危先证者及其家庭成员，从基于人口的明尼苏达州癌症监测系统招募200名高危先证者及其家庭成员。我们将从60个人中 我们将在梅奥诊所收集新鲜的冷冻结直肠癌组织，其家人将根据全面数据收集协议进行招募。我们将对我们最初研究的所有家系进行系统的跟踪，以增强将暴露史、家族史和分子标记与临床结果相关联的能力；我们将为MMR基因分析提供生物谱系；我们将维护梅奥生物谱系和生物信息学系统。 我们建议进行一项先导性轻松对照研究，研究吸烟者和非吸烟者中α-L抗胰蛋白酶缺乏症等位基因杂合性与错配修复缺陷型结直肠癌的风险因素之间的关系。梅奥CFR成员致力于利用CFR-S全面合作创造的机会促进对结直肠癌的了解 其结构、大量参与者及其和谐的调查团队。

DESCRIPTION (provided by applicant): The Mayo Clinic is a founding member of the Cooperative Family Registry (CFR), an NCI-supported consortium of six centers initiated in 1997 to establish a comprehensive collaborative infrastructure to facilitate interdlsciplinary studies of the genetics and epidemiology of colorectal cancer (CRC). Using common data collection protocols and core instruments, the CFR centers recruit CRC probands and their relatives. By the end of the current recruitment phase (July 2002), the CFR will have accrued data and biospecimens from 7,773 probands, 15,232 relatives (affected and unaffected), and more than 2000 unrelated controls, demonstrating the high level of productivity of the CFR as a whole. To fully realize the research potential of the CFR, we collectively propose the following specific alms in the next five years: focused recruitment of (1) high risk families and (2) minorities (African-American and Japanese); (3) systematic follow-up of CFR participants; (4) identification of all carriers of mutations in the DNA mismatch repair (MMR)genes; (5) maintain the CFR biospecimens repository; (6) maintain bioinformatics support activities; (7) establish a fresh frozen tissue repository utilizing the CFR infrastructure. Cost effective ascertainment of large numbers of high-risk families has been a strength of the Mayo CFR design. We have met and exceeded our original aims regarding recruitment of high-risk families and collection of tumor blocks. The Mayo group?s commitment to the CFR as a whole is evidenced by our leadership in writing two competitive supplements that supported registry-wide essential activities (MSI tumor testing and biospecimen processing), our collaborative research activities, and our active role in all CFR working groups. For this renewal, the Mayo CFR proposes to recruit 160 high-risk probands and their family members from the Mayo Clinic Rochester and 200 high-risk probands and their family members from the population-based Minnesota Cancer Surveillance System. We will identify 60 individuals from Mayo Clinic on whom we will collect fresh frozen CRC tissue and whose families will be recruited under the comprehensive data collection protocol. We will conduct systematic follow-up on all our originally studied families to enhance the capacity to correlate exposure histories, family histories, and molecular markers with clinic outcomes; we will provide biospecimens for MMR gene analysis; we will maintain the Mayo biospecimens and bioinformatics systems. We propose a pilot pilot ease-control study of the association of heterozygosity for alpha-l-antitrypsin deficiency alleles as a risk factor for mismatch repair-deficient CRC in smokers and non smokers. The Mayo CFR members are dedicated to advancing knowledge on colorectal cancer using the opportunities created by the CFR?s comprehensive collaborative structure, large numbers of participants, and its harmonious team of investigators.