The objectives of the Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (TSGVC) consortium are to thoroughly investigate and identify susceptibility loci for colorectal cancer, to characterize the biologic basis of inherited susceptibility, and to recognize how genetic variation may be quantified and modified by genetic and environmental risk factors. This long-term goal will be achieved through an integrated design with three highly-related Areas of investigation and an Administrative Core. Within Area 1, the program proposes a combined analysis of five existing genome-wide association studies (GWAS) with approximately 7,000 cases and 7,000 controls, followed by an accelerated, integrated approach to characterize new susceptibility loci in two replication phases. In the first replication phase, 8,000 cases will be genotyped and compared to publicly available data on ~8,000 controls from the Welcome Trust Case Control Consortium. A second replication phase evaluates candidate SNPs in more than 9,000 cases and 9,000 controls to confirm new susceptibility loci, gene by gene interactions, gene by environment interactions, and pathway-based analyses. Within Area 2, the program will establish a comprehensive strategy to study the biological implications of the diverse and robustly replicated associations identified through GWA studies of colorectal cancer, Area 3 develops a framework for understanding how replicated associations are modified by known epidemiologic risk factors for colorectal cancer, estimates the penetrance and population attributable risk of variants, and develops complex risk models that incorporate genetic and environmental risk factors. An Administrative Core coordinates the research and bioinformatic efforts of the investigative team, interacts with other trans-initiative investigators, and facilitates joint activities between NCI and the consortium. The proposed study will identify new genes that predispose to colorectal cancer. Detailed studies will show why these genes predispose to cancer. Complex models that take advantage of this new genetic information together with known environmental factors for colorectal cancer will expedite the translation of these findings into clinical practice and will reduce the public health burden of colorectal cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
7U19CA148107-03
Application #
8330347
Study Section
Special Emphasis Panel (ZCA1-SRLB-4 (J1))
Program Officer
Rogers, Scott
Project Start
2010-08-01
Project End
2014-06-30
Budget Start
2012-09-20
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$2,890,036
Indirect Cost
$745,554
Name
University of Southern California
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Closa, Adria; Cordero, David; Sanz-Pamplona, Rebeca et al. (2014) Identification of candidate susceptibility genes for colorectal cancer through eQTL analysis. Carcinogenesis 35:2039-46
Cheng, Iona; Kocarnik, Jonathan M; Dumitrescu, Logan et al. (2014) Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia. Gut 63:800-7
Wang, Hansong; Burnett, Terrilea; Kono, Suminori et al. (2014) Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. Nat Commun 5:4613
Hazelett, Dennis J; Rhie, Suhn Kyong; Gaddis, Malaina et al. (2014) Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS Genet 10:e1004102
Biancolella, Michela; Fortini, Barbara K; Tring, Stephanie et al. (2014) Identification and characterization of functional risk variants for colorectal cancer mapping to chromosome 11q23.1. Hum Mol Genet 23:2198-209
Du, Mengmeng; Zhang, Xuehong; Hoffmeister, Michael et al. (2014) No evidence of gene-calcium interactions from genome-wide analysis of colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 23:2971-6
Fortini, Barbara K; Tring, Stephanie; Plummer, Sarah J et al. (2014) Multiple functional risk variants in a SMAD7 enhancer implicate a colorectal cancer risk haplotype. PLoS One 9:e111914
Freedman, Matthew L; Monteiro, Alvaro N A; Gayther, Simon A et al. (2011) Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet 43:513-8