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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project with Complex Structure Cooperative Agreement (UM1)
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Special Emphasis Panel (ZCA1-SRLB-3 (O1))
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Schully, Sheri D
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Levine, A Joan; Phipps, Amanda I; Baron, John A et al. (2016) Clinicopathologic Risk Factor Distributions for MLH1 Promoter Region Methylation in CIMP-Positive Tumors. Cancer Epidemiol Biomarkers Prev 25:68-75
Savio, Andrea J; Daftary, Darshana; Dicks, Elizabeth et al. (2016) Promoter methylation of ITF2, but not APC, is associated with microsatellite instability in two populations of colorectal cancer patients. BMC Cancer 16:113
Steel, Emma J; Trainer, Alison H; Heriot, Alexander G et al. (2016) The Experience of Extended Bowel Resection in Individuals With a High Metachronous Colorectal Cancer Risk: A Qualitative Study. Oncol Nurs Forum 43:444-52
Kuroiwa-Trzmielina, Joice; Wang, Fan; Rapkins, Robert W et al. (2016) SNP rs16906252C>T Is an Expression and Methylation Quantitative Trait Locus Associated with an Increased Risk of Developing MGMT-Methylated Colorectal Cancer. Clin Cancer Res 22:6266-6277
Kastrinos, Fay; Ojha, Rohit P; Leenen, Celine et al. (2016) Comparison of Prediction Models for Lynch Syndrome Among Individuals With Colorectal Cancer. J Natl Cancer Inst 108:
Win, Aung Ko; Reece, Jeanette C; Dowty, James G et al. (2016) Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. Int J Cancer 139:1557-63
Siiskonen, Satu; Han, Jiali; Li, Tricia et al. (2016) Alcohol Intake is Associated with Increased Risk of Squamous Cell Carcinoma of the Skin: Three US Prospective Cohort Studies. Nutr Cancer 68:545-53
Win, Aung Ko; Jenkins, Mark A; Dowty, James G et al. (2016) Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. Cancer Epidemiol Biomarkers Prev :
Yang, Baiyu; Thrift, Aaron P; Figueiredo, Jane C et al. (2016) Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer. Cancer Epidemiol 44:1-4
Jarvis, David; Mitchell, Jonathan S; Law, Philip J et al. (2016) Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer. Br J Cancer 115:266-72

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