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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1CA167551-03
Application #
8847681
Study Section
Special Emphasis Panel (ZCA1-SRLB-3 (O1))
Program Officer
Schully, Sheri D
Project Start
2013-05-01
Project End
2018-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
3
Fiscal Year
2015
Total Cost
$2,268,681
Indirect Cost
$68,662
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
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
Jenkins, Mark A; Win, Aung Ko; Templeton, Allyson S et al. (2018) Cohort Profile: The Colon Cancer Family Registry Cohort (CCFRC). Int J Epidemiol 47:387-388i
Dashti, S Ghazaleh; Win, Aung Ko; Hardikar, Sheetal S et al. (2018) Physical activity and the risk of colorectal cancer in Lynch syndrome. Int J Cancer 143:2250-2260
Fennell, Lochlan J; Clendenning, Mark; McKeone, Diane M et al. (2018) RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers. Fam Cancer 17:63-69
Kanga-Parabia, Anaita; Gaff, Clara; Flander, Louisa et al. (2018) Discussions about predictive genetic testing for Lynch syndrome: the role of health professionals and families in decisions to decline. Fam Cancer 17:547-555
Hart, Tae L; Charles, Susan T; Gunaratne, Mekhala et al. (2018) Symptom Severity and Quality of Life Among Long-term Colorectal Cancer Survivors Compared With Matched Control Subjects: A Population-Based Study. Dis Colon Rectum 61:355-363
Choi, Yun-Hee; Lakhal-Chaieb, Lajmi; Kröl, Agnieszka et al. (2018) Risks of Colorectal Cancer and Cancer-Related Mortality in Familial Colorectal Cancer Type X and Lynch Syndrome Families. J Natl Cancer Inst :
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

Showing the most recent 10 out of 159 publications