Colon Cancer Family Registry Cohort

描述（由申请人提供）：国际多中心结肠癌家族登记队列（CCFRC）由10，000多个结直肠癌和其他癌症风险增加的家庭和个人组成。现有的标准化数据包括基线流行病学和随访问卷、临床数据、血液、样本、肿瘤组织块、综合基因型数据，包括相当大比例受试者的全基因组关联研究（GWAS）数据，以及结直肠肿瘤的广泛分子特征。在本申请中，我们寻求资金以支持该队列的基础设施和扩展，具有以下具体目标：目标1：通过以下方式积极随访CCFRC来维持队列：（i）通过问卷和访谈系统地更新个人和家族癌症史以及生命状态，个人风险因素，结肠直肠息肉的患病率以及治疗和癌症复发数据;（ii）验证自基线以来诊断出的所有癌症事件报告;（iii）根据区域和国家死亡登记处核实所有死亡报告;（iv）继续并加强我们随着时间的推移保留队列参与者的最新方法。我们还将保留现有的生物标本库和信息功能。目标二：继续对队列进行分子表征，以最大限度地获取信息并有效促进多种类型的研究：（i）对自基线以来诊断的所有新发结直肠癌病例进行标准化病理学审查;（ii）通过免疫组化、BRAF、K-ras和MLH 1启动子甲基化对新发结直肠癌肿瘤进行亚型分型;（iii）在指示的情况下，对参与者进行DNA错配修复基因和MYH中的已知家族性突变的基因分型;以及（iv）对尚未被GWAS发现和验证的16个SNP进行基因分型的所有参与者进行基因分型。目标3：（i）收集和提取治疗的医疗记录和自开始以来队列中基于人群的结直肠癌病例的复发数据，以及自基线以来在能够以成本有效的方式实现这一点的选定中心的所有结直肠癌事件病例的复发数据;以及（ii）在可能的情况下，策略性地收集高风险参与者的结肠息肉的结肠镜检查和病理学报告（即Lynch综合征、X型和双等位基因MYH携带者）;和（iii）通过问卷调查收集额外的行为数据，这将提高队列的保留率，并促进将CCFRC的发现转化为临床或公共卫生实践。目标4：通过与广大科学界的积极合作，继续扩大对CCFRC及其资源的利用。

DESCRIPTION (provided by applicant): The international, multi-site Colon Cancer Family Registry Cohort (CCFRC) is comprised of over 10,000 families and individuals at increased risk of colorectal and other cancers. Existing standardized data include baseline epidemiologic and follow-up questionnaires, clinical data, blood, samples, tumor blocks, comprehensive genotype data, including genome-wide association study (GWAS) data on a substantial proportion of subjects, and extensive molecular characterization of the colorectal tumors. In this application, we seek funding to support the infrastructure and expansion of this cohort with the following specific aims: Aim 1: Maintain the cohort by active follow-up of the CCFRC by: (i) systematically updating personal and family history of cancer and vital status, personal risk factors, prevalence of colorectal polyps, and treatment and cancer recurrence data through questionnaires and interviews; (ii) validating all reports of incident cancers diagnosed since baseline; and (iii) verifying all reports of death against regional and national death registries; (iv) continuing and enhancing with state-of-the-art approaches our retention of cohort participants over time. We will also maintain the existing Biospecimen Repositories and informatics functions. Aim 2: Continue to molecularly characterize the cohort to maximize information and efficiently facilitate multiple types of research by: (i) conducting standardized pathology review for all incident colorectal cancer cases diagnosed since baseline; (ii) sub typing incident colorectal cancer tumors by immunohistochemistry, BRAF, K-ras, and MLH1 promoter methylation; (iii) genotyping, where indicated, participants for known familial mutations in DNA mismatch repair genes and MYH; and (iv) genotyping all participants who have not yet been genotyped for 16 SNPs discovered and validated by GWAS. Aim 3: Enhancement of the cohort with additional clinical and behavioral data by: (i) collecting and abstracting medical records of treatment and recurrence data on population-based cases of colorectal cancer in the cohort since inception, and on all incident cases of colorectal cancer since baseline in selected centers that are able to accomplish this in a cost-effective manner; and (ii) strategically collecting colonoscopy and pathology reports of colonic polyps when possible for high-risk participants (i.e. Lynch Syndrome, Type X, and bi-allelic MYH carriers); and (iii) collecting additional behavioral data by questionnaire that will enhance retention of the cohort and facilitate the translation of CCFRC discoveries into clinical or public health practice. Aim 4: Continue to expand the use of the CCFRC and its resources through active collaborations with the larger scientific community.