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.
The Colon Cancer Family Registry Cohort is a resource established to facilitate studies worldwide on the causes, prevention, and treatment of colorectal cancer (CRC). It is the largest single family-based resource in the world for the study of CRC (and other cancers that occur in association with CRC). As such, it is critical that this resource is supported since many important studies that may affect clinical and/or public health practice depend on this resource.
|Ten Broeke, Sanne W; van der Klift, Heleen M; Tops, Carli M J et al. (2018) Cancer Risks for PMS2-Associated Lynch Syndrome. J Clin Oncol 36:2961-2968|
|Pande, Mala; Joon, Aron; Brewster, Abenaa M et al. (2018) Genetic susceptibility markers for a breast-colorectal cancer phenotype: Exploratory results from genome-wide association studies. PLoS One 13:e0196245|
|Schmit, Stephanie L; Edlund, Christopher K; Schumacher, Fredrick R et al. (2018) Novel Common Genetic Susceptibility Loci for Colorectal Cancer. J Natl Cancer Inst :|
|Su, Yu-Ru; Di, Chongzhi; Bien, Stephanie et al. (2018) A Mixed-Effects Model for Powerful Association Tests in Integrative Functional Genomics. Am J Hum Genet 102:904-919|
|Pan, Jennifer Y; Haile, Robert W; Templeton, Allyson et al. (2018) Worldwide Practice Patterns in Lynch Syndrome Diagnosis and Management, Based on Data From the International Mismatch Repair Consortium. Clin Gastroenterol Hepatol 16:1901-1910.e11|
|Clendenning, Mark; Huang, Alvin; Jayasekara, Harindra et al. (2018) Somatic mutations of the coding microsatellites within the beta-2-microglobulin gene in mismatch repair-deficient colorectal cancers and adenomas. Fam Cancer 17:91-100|
|Buchanan, Daniel D; Stewart, Jenna R; Clendenning, Mark et al. (2018) Risk of colorectal cancer for carriers of a germ-line mutation in POLE or POLD1. Genet Med 20:890-895|
|Neumeyer, Sonja; Banbury, Barbara L; Arndt, Volker et al. (2018) Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer. Br J Cancer 118:1639-1647|
|Tanskanen, Tomas; van den Berg, Linda; Välimäki, Niko et al. (2018) Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci. Int J Cancer 142:540-546|
|Sheth, Harsh; Northwood, Emma; Ulrich, Cornelia M et al. (2018) Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations. PLoS One 13:e0192223|
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