The USC Consortium, one of the Colon CFR centers, is comprised of a high risk clinic at the Cleveland Clinic and six population-based centers: University of Arizona, University of Colorado, Dartmouth, University of Minnesota, University of North Carolina, and USC. The Colon CFR is dedicated to the maintenance of a comprehensive infrastructure to facilitate collaborative, interdisciplinary studies regarding the etiology, prevention, and clinical management of colorectal cancer (CRC). The current RFA (CA-08-502) is a U24, which is intended to maintain and enhance the core infrastructures of the Colon CFR. In accordance with this mechanism, we have the following specific aims for Phase III. 1) Expand families already in the Colon CFR who carry a deleterious mutation in a mismatch repair (MMR) gene (MLH1, MSH2, or MSH6), which will enable more informative analyses of penetrance and risk factors among carriers. There are 38 such families in the USC Consortium;2) Recruit through the Cleveland Clinic (CCF) 97 additional families who either carry an MMR or MYH mutation or meet Amsterdam I or II criteria. 3) Follow current families with passive and active follow-up every five years to obtain updates on family history of cancer and vital status, pathology reports and tumor blocks on any new CRC cases and HNPCC-related cancers, and informed consents for possible future studies of clinical data. There are 3,709 population-based and 404 clinic-based subjects eligible for follow-up in the USC Consortium as of 11/07;4) Obtain information on stage for all probands for whom it is not already available and obtain an informed consent to obtain copies of selected medical records from all probands to facilitate future clinical studies. At the USC Consortium, we will obtain this information for 1,443 probands;5) Collaborate with the Molecular Characterization Core by dispatching required biospecimens to the Mayo Clinic for immunohistochemistry (IHC) testing of the MLH1, MSH2, and MSH6 proteins, and MMR mutation testing guided by the IHC results, and to the Queensland Institute of Medical Research for testing for somatic mutations in BRAF. MLH1 methylation testing for the Colon CFR will continue in the laboratory of Dr. Peter Laird at USC;6) maintain the biospecimens core, add to the core all new samples from subjects recruited in Phase III, and coordinate future efforts with the Central Repository. In the USC Consortium, to date from Phases I and II combined, we have blood samples from 3,635 subjects and tumor blocks from 1,390 cases;7) maintain the local bioinformatics core and coordinate efforts with RTI. 8) Maintain the administrative core. We can accomplish these proposed aims within the current budget defined in the RFA and doing so will enhance and maintain the core elements of the Colon CFR infrastructure, which is proving to be an outstanding resource for studies of colorectal cancer causes and prevention.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24CA074799-13
Application #
8132331
Study Section
Special Emphasis Panel (ZCA1-SRRB-Y (O1))
Program Officer
Schully, Sheri D
Project Start
1997-09-30
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
13
Fiscal Year
2011
Total Cost
$1,740,161
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
May-Wilson, Sebastian; Sud, Amit; Law, Philip J et al. (2017) Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis. Eur J Cancer 84:228-238
DeRycke, Melissa S; Gunawardena, Shanaka; Balcom, Jessica R et al. (2017) Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes. Mol Genet Genomic Med 5:553-569
Win, Aung Ko; Jenkins, Mark A; Dowty, James G et al. (2017) Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. Cancer Epidemiol Biomarkers Prev 26:404-412
Dashti, S Ghazaleh; Buchanan, Daniel D; Jayasekara, Harindra et al. (2017) Alcohol Consumption and the Risk of Colorectal Cancer for Mismatch Repair Gene Mutation Carriers. Cancer Epidemiol Biomarkers Prev 26:366-375
Lindor, Noralane M; Larson, Melissa C; DeRycke, Melissa S et al. (2017) Germline miRNA DNA variants and the risk of colorectal cancer by subtype. Genes Chromosomes Cancer 56:177-184
Choi, Yun-Hee; Briollais, Laurent; Win, Aung K et al. (2017) Modeling of successive cancer risks in Lynch syndrome families in the presence of competing risks using copulas. Biometrics 73:271-282
Rodriguez-Broadbent, Henry; Law, Philip J; Sud, Amit et al. (2017) Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer. Int J Cancer 140:2701-2708
Orlando, Giulia; Law, Philip J; Palin, Kimmo et al. (2016) Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease. Hum Mol Genet 25:2349-2359
Shang, Jie; Reece, Jeanette C; Buchanan, Daniel D et al. (2016) Cholecystectomy and the risk of colorectal cancer by tumor mismatch repair deficiency status. Int J Colorectal Dis 31:1451-7
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

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