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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
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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.

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Publications

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
Authors: Fehringer G. , Kraft P. , Pharoah P.D. , Eeles R.A. , Chatterjee N. , Schumacher F.R. , Schildkraut J.M. , Lindström S. , Brennan P. , Bickeböller H. , et al. .
Source: Cancer Research, 2016-09-01 00:00:00.0; 76(17), p. 5103-14.
EPub date: 2016-09-01 00:00:00.0.
PMID: 27197191
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Genome-wide Association Study Of Colorectal Cancer In Hispanics
Authors: Schmit S.L. , Schumacher F.R. , Edlund C.K. , Conti D.V. , Ihenacho U. , Wan P. , Van Den Berg D. , Casey G. , Fortini B.K. , Lenz H.J. , et al. .
Source: Carcinogenesis, 2016 06; 37(6), p. 547-56.
PMID: 27207650
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Mendelian randomization study of adiposity-related traits and risk of breast, ovarian, prostate, lung and colorectal cancer.
Authors: Gao C. , Patel C.J. , Michailidou K. , Peters U. , Gong J. , Schildkraut J. , Schumacher F.R. , Zheng W. , Boffetta P. , Stucker I. , et al. .
Source: International Journal Of Epidemiology, 2016 06; 45(3), p. 896-908.
EPub date: 2016-07-17 00:00:00.0.
PMID: 27427428
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Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer.
Authors: Neumeyer S. , Banbury B.L. , Arndt V. , Berndt S.I. , Bezieau S. , Bien S.A. , Buchanan D.D. , Butterbach K. , Caan B.J. , Campbell P.T. , et al. .
Source: British Journal Of Cancer, 2018 Jun; 118(12), p. 1639-1647.
EPub date: 2018-05-24 00:00:00.0.
PMID: 29795306
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Cohort Profile: The Colon Cancer Family Registry Cohort (CCFRC).
Authors: Jenkins M.A. , Win A.K. , Templeton A.S. , Angelakos M.S. , Buchanan D.D. , Cotterchio M. , Figueiredo J.C. , Thibodeau S.N. , Baron J.A. , Potter J.D. , et al. .
Source: International Journal Of Epidemiology, 2018-02-27 00:00:00.0; , .
EPub date: 2018-02-27 00:00:00.0.
PMID: 29490034
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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.
Authors: Tanskanen T. , van den Berg L. , Välimäki N. , Aavikko M. , Ness-Jensen E. , Hveem K. , Wettergren Y. , Bexe Lindskog E. , Tőnisson N. , Metspalu A. , et al. .
Source: International Journal Of Cancer, 2018-02-01 00:00:00.0; 142(3), p. 540-546.
EPub date: 2017-10-12 00:00:00.0.
PMID: 28960316
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Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia.
Authors: Gu F. , Zhang H. , Hyland P.L. , Berndt S. , Gapstur S.M. , Wheeler W. , Ellipse Consortium T. , Amos C.I. , Bezieau S. , Bickeböller H. , et al. .
Source: International Journal Of Cancer, 2017-11-01 00:00:00.0; 141(9), p. 1794-1802.
EPub date: 2017-07-29 00:00:00.0.
PMID: 28699174
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Investigating the genetic relationship between Alzheimer's disease and cancer using GWAS summary statistics.
Authors: Feng Y.A. , Cho K. , Lindstrom S. , Kraft P. , Cormack J. , IGAP Consortium, Colorectal Transdisciplinary Study (CORECT) , Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) , Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) , Transdisciplinary Research in Cancer of the Lung (TRICL) , Liang L. , et al. .
Source: Human Genetics, 2017-08-05 00:00:00.0; , .
EPub date: 2017-08-05 00:00:00.0.
PMID: 28780673
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Estimating the Effect of Targeted Screening Strategies: An Application to Colonoscopy and Colorectal Cancer.
Authors: Thomas D.C. .
Source: Epidemiology (cambridge, Mass.), 2017 Jul; 28(4), p. 470-478.
PMID: 28368944
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Quantifying the genetic correlation between multiple cancer types.
Authors: Lindström S. , Finucane H. , Bulik-Sullivan B. , Schumacher F.R. , Amos C.I. , Hung R.J. , Rand K. , Gruber S.B. , Conti D. , Permuth J.B. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2017-06-21 00:00:00.0; , .
EPub date: 2017-06-21 00:00:00.0.
PMID: 28637796
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Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.
Authors: Wang H. , Schmit S.L. , Haiman C.A. , Keku T.O. , Kato I. , Palmer J.R. , van den Berg D. , Wilkens L.R. , Burnett T. , Conti D.V. , et al. .
Source: International Journal Of Cancer, 2017-06-15 00:00:00.0; 140(12), p. 2728-2733.
EPub date: 2017-06-15 00:00:00.0.
PMID: 28295283
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What Does "Precision Medicine" Have to Say About Prevention?
Authors: Thomas D.C. .
Source: Epidemiology (cambridge, Mass.), 2017-03-29 00:00:00.0; , .
EPub date: 2017-03-29 00:00:00.0.
PMID: 28368942
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Genetic Variants In Epigenetic Pathways And Risks Of Multiple Cancers In The Game-on Consortium
Authors: Toth R. , Scherer D. , Kelemen L.E. , Risch A. , Hazra A. , Balavarca Y. , Issa J.J. , Moreno V. , Eeles R.A. , Ogino S. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2017-01-23 00:00:00.0; , .
PMID: 28115406
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The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.
Authors: Amos C.I. , Dennis J. , Wang Z. , Byun J. , Schumacher F.R. , Gayther S.A. , Casey G. , Hunter D.J. , Sellers T.A. , Gruber S.B. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2017 Jan; 26(1), p. 126-135.
PMID: 27697780
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Telomere Structure And Maintenance Gene Variants And Risk Of Five Cancer Types
Authors: Karami S. , Han Y. , Pande M. , Cheng I. , Rudd J. , Pierce B.L. , Nutter E.L. , Schumacher F.R. , Kote-Jarai Z. , Lindstrom S. , et al. .
Source: International Journal Of Cancer, 2016-12-15 00:00:00.0; 139(12), p. 2655-2670.
PMID: 27459707
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Tumor-Infiltrating Lymphocytes, Crohn's-Like Lymphoid Reaction, and Survival From Colorectal Cancer.
Authors: Rozek L.S. , Schmit S.L. , Greenson J.K. , Tomsho L.P. , Rennert H.S. , Rennert G. , Gruber S.B. .
Source: Journal Of The National Cancer Institute, 2016 Aug; 108(8), .
PMID: 27172903
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Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk.
Authors: Zeng C. , Matsuda K. , Jia W.H. , Chang J. , Kweon S.S. , Xiang Y.B. , Shin A. , Jee S.H. , Kim D.H. , Zhang B. , et al. .
Source: Gastroenterology, 2016 Jun; 150(7), p. 1633-45.
PMID: 26965516
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Mutanome And Expression Of Immune Response Genes In Microsatellite Stable Colon Cancer
Authors: Sanz-Pamplona R. , Gil-Hoyos R. , López-Doriga A. , Alonso M.H. , Aussó S. , Molleví D.G. , Santos C. , Sanjuán X. , Salazar R. , Alemany R. , et al. .
Source: Oncotarget, 2016-04-05 00:00:00.0; 7(14), p. 17711-25.
PMID: 26871478
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Coffee Consumption And The Risk Of Colorectal Cancer
Authors: Schmit S.L. , Rennert H.S. , Rennert G. , Gruber S.B. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Apr; 25(4), p. 634-9.
PMID: 27196095
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Adaptive Set-Based Methods for Association Testing.
Authors: Su Y.C. , Gauderman W.J. , Berhane K. , Lewinger J.P. .
Source: Genetic Epidemiology, 2016 Feb; 40(2), p. 113-22.
PMID: 26707371
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Tests for Gene-Environment Interactions and Joint Effects With Exposure Misclassification.
Authors: Boonstra P.S. , Mukherjee B. , Gruber S.B. , Ahn J. , Schmit S.L. , Chatterjee N. .
Source: American Journal Of Epidemiology, 2016-02-01 00:00:00.0; 183(3), p. 237-47.
EPub date: 2016-02-01 00:00:00.0.
PMID: 26755675
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Common Genetic Variation And Survival After Colorectal Cancer Diagnosis: A Genome-wide Analysis
Authors: Phipps A.I. , Passarelli M.N. , Chan A.T. , Harrison T.A. , Jeon J. , Hutter C.M. , Berndt S.I. , Brenner H. , Caan B.J. , Campbell P.T. , et al. .
Source: Carcinogenesis, 2016 Jan; 37(1), p. 87-95.
PMID: 26586795
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A Cross-cancer Genetic Association Analysis Of The Dna Repair And Dna Damage Signaling Pathways For Lung, Ovary, Prostate, Breast, And Colorectal Cancer
Authors: Scarbrough P.M. , Weber R.P. , Iversen E.S. , Brhane Y. , Amos C.I. , Kraft P. , Hung R.J. , Sellers T.A. , Witte J.S. , Pharoah P. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Jan; 25(1), p. 193-200.
PMID: 26637267
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A Germline Variant On Chromosome 4q31.1 Associates With Susceptibility To Developing Colon Cancer Metastasis
Authors: Markowitz S.D. , Nock N.L. , Schmit S.L. , Stadler Z.K. , Joseph V. , Zhang L. , Willis J.E. , Scacheri P. , Veigl M. , Adams M.D. , et al. .
Source: Plos One, 2016; 11(1), p. e0146435.
PMID: 26751797
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Cross Cancer Genomic Investigation Of Inflammation Pathway For Five Common Cancers: Lung, Ovary, Prostate, Breast, And Colorectal Cancer
Authors: Hung R.J. , Ulrich C.M. , Goode E.L. , Brhane Y. , Muir K. , Chan A.T. , Marchand L.L. , Schildkraut J. , Witte J.S. , Eeles R. , et al. .
Source: Journal Of The National Cancer Institute, 2015 Nov; 107(11), .
PMID: 26319099
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Exome Sequencing Reveals Amer1 As A Frequently Mutated Gene In Colorectal Cancer
Authors: Sanz-Pamplona R. , Lopez-Doriga A. , Paré-Brunet L. , Lázaro K. , Bellido F. , Alonso M.H. , Aussó S. , Guinó E. , Beltrán S. , Castro-Giner F. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2015-10-15 00:00:00.0; 21(20), p. 4709-18.
PMID: 26071483
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The Influence Of Screening For Precancerous Lesions On Family-based Genetic Association Tests: An Example Of Colorectal Polyps And Cancer
Authors: Schmit S.L. , Figueiredo J.C. , Cortessis V.K. , Thomas D.C. .
Source: American Journal Of Epidemiology, 2015-10-15 00:00:00.0; 182(8), p. 714-22.
PMID: 26306664
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Genetic Determinants Of Telomere Length And Risk Of Common Cancers: A Mendelian Randomization Study
Authors: Zhang C. , Doherty J.A. , Burgess S. , Hung R.J. , Lindström S. , Kraft P. , Gong J. , Amos C.I. , Sellers T.A. , Monteiro A.N. , et al. .
Source: Human Molecular Genetics, 2015-09-15 00:00:00.0; 24(18), p. 5356-66.
PMID: 26138067
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Genome-wide association study of colorectal cancer identifies six new susceptibility loci.
Authors: Schumacher F.R. , Schmit S.L. , Jiao S. , Edlund C.K. , Wang H. , Zhang B. , Hsu L. , Huang S.C. , Fischer C.P. , Harju J.F. , et al. .
Source: Nature Communications, 2015-07-07 00:00:00.0; 6, p. 7138.
EPub date: 2015-07-07 00:00:00.0.
PMID: 26151821
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A Model To Determine Colorectal Cancer Risk Using Common Genetic Susceptibility Loci
Authors: Hsu L. , Jeon J. , Brenner H. , Gruber S.B. , Schoen R.E. , Berndt S.I. , Chan A.T. , Chang-Claude J. , Du M. , Gong J. , et al. .
Source: Gastroenterology, 2015 Jun; 148(7), p. 1330-9.e14.
PMID: 25683114
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The impact of exposure-biased sampling designs on detection of gene-environment interactions in case-control studies with potential exposure misclassification.
Authors: Stenzel S.L. , Ahn J. , Boonstra P.S. , Gruber S.B. , Mukherjee B. .
Source: European Journal Of Epidemiology, 2015 May; 30(5), p. 413-23.
PMID: 24894824
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Microrna Polymorphisms And Risk Of Colorectal Cancer
Authors: Schmit S.L. , Gollub J. , Shapero M.H. , Huang S.C. , Rennert H.S. , Finn A. , Rennert G. , Gruber S.B. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Jan; 24(1), p. 65-72.
PMID: 25342389
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Corrigendum: Genome-wide Association Study Of Colorectal Cancer Identifies Six New Susceptibility Loci
Authors: Schumacher F.R. , Schmit S.L. , Jiao S. , Edlund C.K. , Wang H. , Zhang B. , Hsu L. , Huang S.C. , Fischer C.P. , Harju J.F. , et al. .
Source: Nature Communications, 2015; 6, p. 8739.
PMID: 26498495
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No evidence of gene-calcium interactions from genome-wide analysis of colorectal cancer risk.
Authors: Du M. , Zhang X. , Hoffmeister M. , Schoen R.E. , Baron J.A. , Berndt S.I. , Brenner H. , Carlson C.S. , Casey G. , Chan A.T. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2014 Dec; 23(12), p. 2971-6.
PMID: 25192705
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A Novel Colorectal Cancer Risk Locus At 4q32.2 Identified From An International Genome-wide Association Study
Authors: Schmit S.L. , Schumacher F.R. , Edlund C.K. , Conti D.V. , Raskin L. , Lejbkowicz F. , Pinchev M. , Rennert H.S. , Jenkins M.A. , Hopper J.L. , et al. .
Source: Carcinogenesis, 2014 Nov; 35(11), p. 2512-9.
PMID: 25023989
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Identification Of Candidate Susceptibility Genes For Colorectal Cancer Through Eqtl Analysis
Authors: Closa A. , Cordero D. , Sanz-Pamplona R. , Solé X. , Crous-Bou M. , Paré-Brunet L. , Berenguer A. , Guino E. , Lopez-Doriga A. , Guardiola J. , et al. .
Source: Carcinogenesis, 2014 Sep; 35(9), p. 2039-46.
PMID: 24760461
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Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.
Authors: Wang H. , Burnett T. , Kono S. , Haiman C.A. , Iwasaki M. , Wilkens L.R. , Loo L.W. , Van Den Berg D. , Kolonel L.N. , Henderson B.E. , et al. .
Source: Nature Communications, 2014-08-08 00:00:00.0; 5, p. 4613.
EPub date: 2014-08-08 00:00:00.0.
PMID: 25105248
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Pleiotropic Effects Of Genetic Risk Variants For Other Cancers On Colorectal Cancer Risk: Page, Gecco And Ccfr Consortia
Authors: Cheng I. , Kocarnik J.M. , Dumitrescu L. , Lindor N.M. , Chang-Claude J. , Avery C.L. , Caberto C.P. , Love S.A. , Slattery M.L. , Chan A.T. , et al. .
Source: Gut, 2014 May; 63(5), p. 800-7.
PMID: 23935004
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Identification And Characterization Of Functional Risk Variants For Colorectal Cancer Mapping To Chromosome 11q23.1
Authors: Biancolella M. , Fortini B.K. , Tring S. , Plummer S.J. , Mendoza-Fandino G.A. , Hartiala J. , Hitchler M.J. , Yan C. , Schumacher F.R. , Conti D.V. , et al. .
Source: Human Molecular Genetics, 2014-04-15 00:00:00.0; 23(8), p. 2198-209.
PMID: 24256810
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Invited Commentary: Is It Time To Retire The "pack-years" Variable? Maybe Not!
Authors: Thomas D.C. .
Source: American Journal Of Epidemiology, 2014-02-01 00:00:00.0; 179(3), p. 299-302.
PMID: 24355333
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Comprehensive Functional Annotation Of 77 Prostate Cancer Risk Loci
Authors: Hazelett D.J. , Rhie S.K. , Gaddis M. , Yan C. , Lakeland D.L. , Coetzee S.G. , Ellipse/GAME-ON consortium , Practical consortium , Henderson B.E. , Noushmehr H. , et al. .
Source: Plos Genetics, 2014 Jan; 10(1), p. e1004102.
PMID: 24497837
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Functional annotation of putative regulatory elements at cancer susceptibility Loci.
Authors: Rosse S.A. , Auer P.L. , Carlson C.S. .
Source: Cancer Informatics, 2014; 13(Suppl 2), p. 5-17.
PMID: 25288875
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Multiple Functional Risk Variants In A Smad7 Enhancer Implicate A Colorectal Cancer Risk Haplotype
Authors: Fortini B.K. , Tring S. , Plummer S.J. , Edlund C.K. , Moreno V. , Bresalier R.S. , Barry E.L. , Church T.R. , Figueiredo J.C. , Casey G. .
Source: Plos One, 2014; 9(11), p. e111914.
PMID: 25375357
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Measurement Error In Spatial Exposure Models: Study Design Implications
Authors: Thomas D.C. .
Source: Environmetrics, 2013-12-01 00:00:00.0; 24(8), p. 518-520.
PMID: 24729740
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Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.
Authors: Peters U. , Jiao S. , Schumacher F.R. , Hutter C.M. , Aragaki A.K. , Baron J.A. , Berndt S.I. , Bézieau S. , Brenner H. , Butterbach K. , et al. .
Source: Gastroenterology, 2013 Apr; 144(4), p. 799-807.e24.
PMID: 23266556
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Confounding And Heterogeneity In Genetic Association Studies With Admixed Populations
Authors: Liu J. , Lewinger J.P. , Gilliland F.D. , Gauderman W.J. , Conti D.V. .
Source: American Journal Of Epidemiology, 2013-02-15 00:00:00.0; 177(4), p. 351-60.
PMID: 23334005
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Two-phase And Family-based Designs For Next-generation Sequencing Studies
Authors: Thomas D.C. , Yang Z. , Yang F. .
Source: Frontiers In Genetics, 2013; 4, p. 276.
PMID: 24379824
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Mlh1 Methylation Screening Is Effective In Identifying Epimutation Carriers
Authors: Pineda M. , Mur P. , Iniesta M.D. , Borrŕs E. , Campos O. , Vargas G. , Iglesias S. , Fernández A. , Gruber S.B. , Lázaro C. , et al. .
Source: European Journal Of Human Genetics : Ejhg, 2012 Dec; 20(12), p. 1256-64.
PMID: 22763379
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Analysis And Optimal Design For Association Studies Using Next-generation Sequencing With Case-control Pools
Authors: Liang W.E. , Thomas D.C. , Conti D.V. .
Source: Genetic Epidemiology, 2012 Dec; 36(8), p. 870-81.
PMID: 22972696
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A Pooled Analysis Of Smoking And Colorectal Cancer: Timing Of Exposure And Interactions With Environmental Factors
Authors: Gong J. , Hutter C. , Baron J.A. , Berndt S. , Caan B. , Campbell P.T. , Casey G. , Chan A.T. , Cotterchio M. , Fuchs C.S. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2012 Nov; 21(11), p. 1974-85.
PMID: 23001243
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