Skip Navigation
Grant Details

Grant Number: 5U19CA148107-04 Interpret this number
Primary Investigator: Gruber, Stephen
Organization: University Of Southern California
Project Title: Transdisciplinary Studies of Genetic Variation in Colorectal Cancer
Fiscal Year: 2013
Back to top


Abstract

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.

Back to top


Publications

Comprehensive functional annotation of 77 prostate cancer risk loci.
Authors: Hazelett DJ, Rhie SK, Gaddis M, Yan C, Lakeland DL, Coetzee SG, Ellipse/GAME-ON consortium, Practical consortium, Henderson BE, Noushmehr H, Cozen W, Kote-Jarai Z, Eeles RA, Easton DF, Haiman CA, Lu W, Farnham PJ, Coetzee GA
Source: PLoS Genet, 2014 Jan;10(1), p. e1004102.
EPub date: 2014 Jan 30.
PMID: 24497837
Related Citations

Back to top


Identification and characterization of functional risk variants for colorectal cancer mapping to chromosome 11q23.1.
Authors: Biancolella M, Fortini BK, Tring S, Plummer SJ, Mendoza-Fandino GA, Hartiala J, Hitchler MJ, Yan C, Schumacher FR, Conti DV, Edlund CK, Noushmehr H, Coetzee SG, Bresalier RS, Ahnen DJ, Barry EL, Berman BP, Rice JC, Coetzee GA, Casey G
Source: Hum Mol Genet, 2014 Apr 15;23(8), p. 2198-209.
EPub date: 2013 Nov 20.
PMID: 24256810
Related Citations

Back to top


Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.
Authors: Cheng I, Kocarnik JM, Dumitrescu L, Lindor NM, Chang-Claude J, Avery CL, Caberto CP, Love SA, Slattery ML, Chan AT, Baron JA, Hindorff LA, Park SL, Schumacher FR, Hoffmeister M, Kraft P, Butler AM, Duggan DJ, Hou L, Carlson CS, Monroe KR, Lin Y, Carty CL, Mann S, Ma J, Giovannucci EL, Fuchs CS, Newcomb PA, Jenkins MA, Hopper JL, Haile RW, Conti DV, Campbell PT, Potter JD, Caan BJ, Schoen RE, Hayes RB, Chanock SJ, Berndt SI, Küry S, Bézieau S, Ambite JL, Kumaraguruparan G, Richardson DM, Goodloe RJ, Dilks HH, Baker P, Zanke BW, Lemire M, Gallinger S, Hsu L, Jiao S, Harrison TA, Seminara D, Haiman CA, Kooperberg C, Wilkens LR, Hutter CM, White E, Crawford DC, Heiss G, Hudson TJ, Brenner H, Bush WS, Casey G, Le Marchand L, Peters U
Source: Gut, 2014 May;63(5), p. 800-7.
EPub date: 2013 Aug 9.
PMID: 23935004
Related Citations

Back to top


Joint analysis for integrating two related studies of different data types and different study designs using hierarchical modeling approaches.
Authors: Li R, Conti DV, Diaz-Sanchez D, Gilliland F, Thomas DC
Source: Hum Hered, 2012;74(2), p. 83-96.
EPub date: 2013 Jan 18.
PMID: 23343600
Related Citations

Back to top


Confounding and heterogeneity in genetic association studies with admixed populations.
Authors: Liu J, Lewinger JP, Gilliland FD, Gauderman WJ, Conti DV
Source: Am J Epidemiol, 2013 Feb 15;177(4), p. 351-60.
EPub date: 2013 Jan 18.
PMID: 23334005
Related Citations

Back to top


Genome-wide search for gene-gene interactions in colorectal cancer.
Authors: Jiao S, Hsu L, Berndt S, Bézieau S, Brenner H, Buchanan D, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock S, Conti DV, Curtis KR, Duggan D, Gallinger S, Gruber SB, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Hopper JL, Hudson TJ, Hutter CM, Jackson RD, Jenkins MA, Kantor ED, Kolonel LN, Küry S, Le Marchand L, Lemire M, Newcomb PA, Potter JD, Qu C, Rosse SA, Schoen RE, Schumacher FR, Seminara D, Slattery ML, Ulrich CM, Zanke BW, Peters U
Source: PLoS One, 2012;7(12), p. e52535.
EPub date: 2012 Dec 26.
PMID: 23300701
Related Citations

Back to top


Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.
Authors: Peters U, Jiao S, Schumacher FR, Hutter CM, Aragaki AK, Baron JA, Berndt SI, Bézieau S, Brenner H, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock SJ, Chen LS, Coetzee GA, Coetzee SG, Conti DV, Curtis KR, Duggan D, Edwards T, Fuchs CS, Gallinger S, Giovannucci EL, Gogarten SM, Gruber SB, Haile RW, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Hopper JL, Hudson TJ, Hunter DJ, Jackson RD, Jee SH, Jenkins MA, Jia WH, Kolonel LN, Kooperberg C, Küry S, Lacroix AZ, Laurie CC, Laurie CA, Le Marchand L, Lemire M, Levine D, Lindor NM, Liu Y, Ma J, Makar KW, Matsuo K, Newcomb PA, Potter JD, Prentice RL, Qu C, Rohan T, Rosse SA, Schoen RE, Seminara D, Shrubsole M, Shu XO, Slattery ML, Taverna D, Thibodeau SN, Ulrich CM, White E, Xiang Y, Zanke BW, Zeng YX, Zhang B, Zheng W, Hsu L, Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium
Source: Gastroenterology, 2013 Apr;144(4), p. 799-807.e24.
EPub date: 2012 Dec 22.
PMID: 23266556
Related Citations

Back to top


A pooled analysis of smoking and colorectal cancer: timing of exposure and interactions with environmental factors.
Authors: Gong J, Hutter C, Baron JA, Berndt S, Caan B, Campbell PT, Casey G, Chan AT, Cotterchio M, Fuchs CS, Gallinger S, Giovannucci E, Harrison T, Hayes R, Hsu L, Jiao S, Lin Y, Lindor NM, Newcomb P, Pflugeisen B, Phipps AI, Rohan T, Schoen R, Seminara D, Slattery ML, Stelling D, Thomas F, Warnick G, White E, Potter J, Peters U
Source: Cancer Epidemiol Biomarkers Prev, 2012 Nov;21(11), p. 1974-85.
EPub date: 2012 Sep 20.
PMID: 23001243
Related Citations

Back to top


Analysis and Optimal Design for Association Studies Using Next-Generation Sequencing With Case-Control Pools.
Authors: Liang WE, Thomas DC, Conti DV
Source: Genet Epidemiol, 2012 Sep 12;null, p. null.
EPub date: 2012 Sep 12.
PMID: 22972696
Related Citations

Back to top


Simultaneously testing for marginal genetic association and gene-environment interaction.
Authors: Dai JY, Logsdon BA, Huang Y, Hsu L, Reiner AP, Prentice RL, Kooperberg C
Source: Am J Epidemiol, 2012 Jul 15;176(2), p. 164-73.
EPub date: 2012 Jul 6.
PMID: 22771729
Related Citations

Back to top


Powerful cocktail methods for detecting genome-wide gene-environment interaction.
Authors: Hsu L, Jiao S, Dai JY, Hutter C, Peters U, Kooperberg C
Source: Genet Epidemiol, 2012 Apr;36(3), p. 183-94.
PMID: 22714933
Related Citations

Back to top


Instrumental variable estimation of the causal effect of plasma 25-hydroxy-vitamin D on colorectal cancer risk: a mendelian randomization analysis.
Authors: Theodoratou E, Palmer T, Zgaga L, Farrington SM, McKeigue P, Din FV, Tenesa A, Davey-Smith G, Dunlop MG, Campbell H
Source: PLoS One, 2012;7(6), p. e37662.
EPub date: 2012 Jun 6.
PMID: 22701574
Related Citations

Back to top


FunciSNP: an R/bioconductor tool integrating functional non-coding data sets with genetic association studies to identify candidate regulatory SNPs.
Authors: Coetzee SG, Rhie SK, Berman BP, Coetzee GA, Noushmehr H
Source: Nucleic Acids Res, 2012 Oct;40(18), p. e139.
EPub date: 2012 Jun 8.
PMID: 22684628
Related Citations

Back to top


Characterization of gene-environment interactions for colorectal cancer susceptibility loci.
Authors: Hutter CM, Chang-Claude J, Slattery ML, Pflugeisen BM, Lin Y, Duggan D, Nan H, Lemire M, Rangrej J, Figueiredo JC, Jiao S, Harrison TA, Liu Y, Chen LS, Stelling DL, Warnick GS, Hoffmeister M, Küry S, Fuchs CS, Giovannucci E, Hazra A, Kraft P, Hunter DJ, Gallinger S, Zanke BW, Brenner H, Frank B, Ma J, Ulrich CM, White E, Newcomb PA, Kooperberg C, LaCroix AZ, Prentice RL, Jackson RD, Schoen RE, Chanock SJ, Berndt SI, Hayes RB, Caan BJ, Potter JD, Hsu L, Bézieau S, Chan AT, Hudson TJ, Peters U
Source: Cancer Res, 2012 Apr 15;72(8), p. 2036-44.
EPub date: 2012 Feb 24.
PMID: 22367214
Related Citations

Back to top


Genetic epidemiology with a capital E: where will we be in another 10 years?
Authors: Thomas DC
Source: Genet Epidemiol, 2012 Apr;36(3), p. 179-82.
EPub date: 2012 Feb 6.
PMID: 22311722
Related Citations

Back to top


Genetic polymorphisms in fatty acid metabolism genes and colorectal cancer.
Authors: Crous-Bou M, Rennert G, Salazar R, Rodriguez-Moranta F, Rennert HS, Lejbkowicz F, Kopelovich L, Lipkin SM, Gruber SB, Moreno V
Source: Mutagenesis, 2012 Mar;27(2), p. 169-76.
PMID: 22294764
Related Citations

Back to top


Some surprising twists on the road to discovering the contribution of rare variants to complex diseases.
Authors: Thomas DC
Source: Hum Hered, 2012;74(3-4), p. 113-7.
EPub date: 2013 Apr 11.
PMID: 23594489
Related Citations

Back to top


Incorporating model uncertainty in detecting rare variants: the Bayesian risk index.
Authors: Quintana MA, Berstein JL, Thomas DC, Conti DV
Source: Genet Epidemiol, 2011 Nov;35(7), p. 638-49.
EPub date: 2011 Aug 26.
PMID: 22009789
Related Citations

Back to top


Using extreme phenotype sampling to identify the rare causal variants of quantitative traits in association studies.
Authors: Li D, Lewinger JP, Gauderman WJ, Murcray CE, Conti D
Source: Genet Epidemiol, 2011 Dec;35(8), p. 790-9.
EPub date: 2011 Sep 15.
PMID: 21922541
Related Citations

Back to top


Meta-analysis of new genome-wide association studies of colorectal cancer risk.
Authors: Peters U, Hutter CM, Hsu L, Schumacher FR, Conti DV, Carlson CS, Edlund CK, Haile RW, Gallinger S, Zanke BW, Lemire M, Rangrej J, Vijayaraghavan R, Chan AT, Hazra A, Hunter DJ, Ma J, Fuchs CS, Giovannucci EL, Kraft P, Liu Y, Chen L, Jiao S, Makar KW, Taverna D, Gruber SB, Rennert G, Moreno V, Ulrich CM, Woods MO, Green RC, Parfrey PS, Prentice RL, Kooperberg C, Jackson RD, Lacroix AZ, Caan BJ, Hayes RB, Berndt SI, Chanock SJ, Schoen RE, Chang-Claude J, Hoffmeister M, Brenner H, Frank B, Bézieau S, Küry S, Slattery ML, Hopper JL, Jenkins MA, Le Marchand L, Lindor NM, Newcomb PA, Seminara D, Hudson TJ, Duggan DJ, Potter JD, Casey G
Source: Hum Genet, 2012 Feb;131(2), p. 217-34.
EPub date: 2011 Jul 15.
PMID: 21761138
Related Citations

Back to top


Principles for the post-GWAS functional characterization of cancer risk loci.
Authors: Freedman ML, Monteiro AN, Gayther SA, Coetzee GA, Risch A, Plass C, Casey G, De Biasi M, Carlson C, Duggan D, James M, Liu P, Tichelaar JW, Vikis HG, You M, Mills IG
Source: Nat Genet, 2011 Jun;43(6), p. 513-8.
PMID: 21614091
Related Citations

Back to top


High risk of colorectal and endometrial cancer in Ashkenazi families with the MSH2 A636P founder mutation.
Authors: Mukherjee B, Rennert G, Ahn J, Dishon S, Lejbkowicz F, Rennert HS, Shiovitz S, Moreno V, Gruber SB
Source: Gastroenterology, 2011 Jun;140(7), p. 1919-26.
EPub date: 2011 Mar 16.
PMID: 21419771
Related Citations

Back to top