Colon Cancer Family Registry Cohort

结肠癌家族登记队列

• 批准号: 9087168
• 负责人: ROBERT William HAILE
• 金额: $ 224.53万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9087168
• 关键词: Affect; BRAF gene; Behavior Therapy; Behavioral; Blood specimen; Cancer Prevention Trial; Cessation of life; Clinical; Clinical Data; Collaborations; Colonic Polyps; Colonoscopy; Colorectal; Colorectal Cancer; Colorectal Neoplasms; Colorectal Polyp; Communication Programs; Communities; DNA; Data; Diagnosis; Ensure; Environmental Risk Factor; Epidemiology; Family; Family history of; Family member; Funding; Future; Genes; Genotype; Hereditary Nonpolyposis Colorectal Neoplasms; High-Risk Cancer; Immunohistochemistry; Individual; Informatics; International; Interview; Investigation; KRAS2 gene; MLH1 gene; Malignant Neoplasms; Medical Records; Methylation; Mismatch Repair; Molecular; Mutation; Neoplasms; Outcome; Participant; Pathology; Pathology Report; Prevalence; Prevention; Public Health; Public Health Practice; Questionnaires; Recurrence; Registries; Reporting; Research; Research Infrastructure; Resources; Risk; Risk Factors; Science; Site; Structure; Time; Translations; Update; Vital Status; Woman; abstracting; base; cancer diagnosis; cancer recurrence; cohort; colon cancer family registry; cost effective; cost efficient; follow-up; gene discovery; genetic risk factor; genome wide association study; high risk; member; men; neoplasm registry; novel; population based; promoter; repository; tumor

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.

描述（由申请人提供）：国际多站点结肠癌家族登记队列（CCFRC）由超过10,000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、肿瘤块、综合基因型数据，包括相当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表征。在本申请中，我们寻求资金支持该队列的基础设施和扩展，具体目标如下：目标1：通过CCFRC的积极随访来维持该队列：(i)通过问卷调查和访谈系统地更新个人和家族癌症史和生命状况、个人风险因素、结肠直肠息肉患病率、治疗和癌症复发数据；（ii）验证自基线以来诊断的所有癌症事件报告；（三）对照区域和国家死亡登记核实所有死亡报告；（iv）随着时间的推移，继续使用最先进的方法并加强我们对队列参与者的保留。我们亦会维持现有的生物标本库及资讯功能。目标2：继续对队列进行分子表征，以最大限度地获取信息，并有效地促进多种类型的研究：(i)对自基线以来诊断的所有结直肠癌病例进行标准化病理审查；（ii）通过免疫组织化学、BRAF、K-ras和MLH1启动子甲基化对结直肠癌肿瘤进行亚分；（iii）基因分型，如有指示，参与者在DNA错配修复基因和MYH中已知的家族突变；（iv）对所有尚未对GWAS发现并验证的16个snp进行基因分型的参与者进行基因分型。目标3：通过以下方式通过额外的临床和行为数据加强队列：(i)收集和提取队列中自成立以来以人群为基础的结直肠癌病例的治疗和复发数据的医疗记录，以及能够以具有成本效益的方式完成这一任务的选定中心中自基线以来所有结直肠癌事件病例的医疗记录；（ii）在可能的情况下战略性地收集高风险参与者（即Lynch综合征、X型和双等位基因MYH携带者）结肠息肉的结肠镜检查和病理报告；（iii）通过问卷调查收集额外的行为数据，这将提高队列的留存率，并促进将CCFRC的发现转化为临床或公共卫生实践。目标4：通过与更大的科学界积极合作，继续扩大CCFRC及其资源的使用。