Familial Colorectal Neoplasia Collaborative Group

描述（由申请人提供）： 马约诊所是合作家庭登记处（CFR）的创始成员之一，CFR是一个由六个中心组成的NCI支持的联盟，成立于1997年，旨在建立一个全面的合作基础设施，以促进结直肠癌（CRC）遗传学和流行病学的跨学科研究。使用通用的数据收集协议和核心工具，CFR中心招募CRC先证者及其亲属。到目前的招募阶段结束时（2002年7月），CFR将从7，773名先证者、15，232名亲属（受影响和未受影响）和2000多名无关对照中积累数据和生物标本，证明CFR作为一个整体的高水平生产力。为了充分发挥CFR的研究潜力，我们共同提出了以下具体的施舍在未来五年：重点招募（1）高风险家庭和（2）少数民族（非洲裔美国人和 日语）;（3）对CFR参与者进行系统随访;（4）识别DNA错配修复（MMR）基因突变的所有携带者;（5）维护CFR生物标本库;（6）维护生物信息学支持活动;（7）利用CFR基础设施建立新鲜冷冻组织库。 对大量高风险家庭的成本效益确认一直是马约CFR设计的优势。我们已经达到并超过了招募高危家庭和收集肿瘤块的最初目标。马约集团？我们在撰写两份竞争性补充材料方面的领导地位证明了我们对CFR的承诺，这两份补充材料支持了注册范围内的基本活动（MSI肿瘤检测和生物标本处理），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。对于此次更新，马约CFR建议从马约诊所罗切斯特招募160名高风险先证者及其家庭成员，从基于人群的明尼苏达州癌症监测系统招募200名高风险先证者及其家庭成员。我们将确定60个人， 我们将收集马约诊所的新鲜冷冻CRC组织，并将根据综合数据收集方案招募其家属。我们将对我们最初研究的所有家族进行系统随访，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;我们将提供用于MMR基因分析的生物标本;我们将维护马约生物标本和生物信息学系统。 我们提出了一个试点容易控制的研究，α-l-抗胰蛋白酶缺乏等位基因的杂合性作为一个风险因素，在吸烟者和非吸烟者的错配修复缺陷型大肠癌。马约CFR成员致力于利用CFR？全面合作 结构，大量的参与者，以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.