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Grant Details

Grant Number: 5R01CA081488-10 Interpret this number
Primary Investigator: Gruber, Stephen
Organization: University Of Michigan
Project Title: Molecular Epidemiology of Colorectal Cancer
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): The Molecular Epidemiology of Colorectal Cancer (MECC) study is a population-based case-control study that examines the contribution of genetic sequence variation and environmental factors to the risk, pathogenesis, and prognosis of colorectal cancer (CRC). CRC is the second leading cause of cancer death in the United States and the leading cause of cancer death in Israel. Epidemiologic risk factors for CRC are reasonably well described, yet the majority of CRC arises in individuals with no known risk factors other than older age. Low penetrance susceptibility alleles such as APC 11307K are likely to play an important role in the population dynamics of this complex disease, yet the genetic variation that contributes to CRC is largely unexplored. Thus the broad objective of the MECC study is to understand how classic epidemiologic factors and genetic variation are related to the risk, pathogenesis, and prognosis of CRC. Israel has a well-defined population structure that facilitates gene discovery, and the differences in the incidence of CRC among different populations within Israel provide an epidemiologic context to study environmental and genetic contributions to CRC. In this collaborative study between the University of Michigan and the National Center for Cancer Control at Carmel Medical Center in Haifa, Israel we plan to evaluate 2 hypotheses: 1) Clinical features, somatic molecular markers, and tumor expression profiles predict relapse-free survival, disease-specific survival, and overall survival, 2) Previously unrecognized genes contribute to the risk of colorectal cancer and can be identified using a whole genome association. These hypotheses will be evaluated through the following specific aims: 1) Discover novel prognostic factors for CRC recurrence and survival of the MECC cases using clinical, laboratory, and epidemiologic data in conjunction with expression profiles of snap frozen tumors, and 2) Complete a whole genome association study of CRC using 400,000 carefully selected single nucleotide polymorphism (SNPs) that are densely spaced in and around approximately 85% of all known human genes.

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Publications

Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.
Authors: Wang H, Burnett T, Kono S, Haiman CA, Iwasaki M, Wilkens LR, Loo LW, Van Den Berg D, Kolonel LN, Henderson BE, Keku TO, Sandler RS, Signorello LB, Blot WJ, Newcomb PA, Pande M, Amos CI, West DW, Bézieau S, Berndt SI, Zanke BW, Hsu L, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Lindor NM, Haile RW, Hopper JL, Jenkins MA, Gallinger S, Casey G, Colon Cancer Family Registry (CCFR), Stenzel SL, Schumacher FR, Peters U, Gruber SB, Colorectal Transdisciplinary Study (CORECT), Tsugane S, Stram DO, Le Marchand L
Source: Nat Commun, 2014 Aug 8;5, p. 4613.
EPub date: 2014 Aug 8.
PMID: 25105248
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Polymorphisms in alcohol metabolism genes ADH1B and ALDH2, alcohol consumption and colorectal cancer.
Authors: Crous-Bou M, Rennert G, Cuadras D, Salazar R, Cordero D, Saltz Rennert H, Lejbkowicz F, Kopelovich L, Monroe Lipkin S, Bernard Gruber S, Moreno V
Source: PLoS One, 2013;8(11), p. e80158.
EPub date: 2013 Nov 25.
PMID: 24282520
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Inflammatory bowel disease and familial adenomatous polyposis.
Authors: Samadder NJ, Gornick M, Everett J, Greenson JK, Gruber SB
Source: J Crohns Colitis, 2013 Apr 1;7(3), p. e103-7.
EPub date: 2012 Jul 17.
PMID: 22809634
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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
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Logistic regression analysis of biomarker data subject to pooling and dichotomization.
Authors: Zhang Z, Liu A, Lyles RH, Mukherjee B
Source: Stat Med, 2012 Sep 28;31(22), p. 2473-84.
EPub date: 2011 Sep 23.
PMID: 21953741
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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
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AXIN2-associated autosomal dominant ectodermal dysplasia and neoplastic syndrome.
Authors: Marvin ML, Mazzoni SM, Herron CM, Edwards S, Gruber SB, Petty EM
Source: Am J Med Genet A, 2011 Apr;155A(4), p. 898-902.
EPub date: 2011 Mar 17.
PMID: 21416598
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A review of statistical methods for testing genetic anticipation: looking for an answer in Lynch syndrome.
Authors: Boonstra PS, Gruber SB, Raymond VM, Huang SC, Timshel S, Nilbert M, Mukherjee B
Source: Genet Epidemiol, 2010 Nov;34(7), p. 756-68.
PMID: 20878717
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MLH1 founder mutations with moderate penetrance in Spanish Lynch syndrome families.
Authors: Borrŕs E, Pineda M, Blanco I, Jewett EM, Wang F, Teulé A, Caldés T, Urioste M, Martínez-Bouzas C, Brunet J, Balmańa J, Torres A, Ramón y Cajal T, Sanz J, Pérez-Cabornero L, Castellví-Bel S, Alonso A, Lanas A, González S, Moreno V, Gruber SB, Rosenberg NA, Mukherjee B, Lázaro C, Capellá G
Source: Cancer Res, 2010 Oct 1;70(19), p. 7379-91.
EPub date: 2010 Sep 21.
PMID: 20858721
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Missing exposure data in stereotype regression model: application to matched case-control study with disease subclassification.
Authors: Ahn J, Mukherjee B, Gruber SB, Sinha S
Source: Biometrics, 2011 Jun;67(2), p. 546-58.
EPub date: 2010 Jun 16.
PMID: 20560931
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Allele-specific expression of APC in adenomatous polyposis families.
Authors: Castellsagué E, González S, Guinó E, Stevens KN, Borrŕs E, Raymond VM, Lázaro C, Blanco I, Gruber SB, Capellá G
Source: Gastroenterology, 2010 Aug;139(2), p. 439-47, 447.e1.
EPub date: 2010 Apr 29.
PMID: 20434453
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Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer.
Authors: Lipkin SM, Chao EC, Moreno V, Rozek LS, Rennert H, Pinchev M, Dizon D, Rennert G, Kopelovich L, Gruber SB
Source: Cancer Prev Res (Phila), 2010 May;3(5), p. 597-603.
EPub date: 2010 Apr 19.
PMID: 20403997
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Smoking, gender, and ethnicity predict somatic BRAF mutations in colorectal cancer.
Authors: Rozek LS, Herron CM, Greenson JK, Moreno V, Capella G, Rennert G, Gruber SB
Source: Cancer Epidemiol Biomarkers Prev, 2010 Mar;19(3), p. 838-43.
EPub date: 2010 Mar 3.
PMID: 20200438
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Human papillomavirus is not associated with colorectal cancer in a large international study.
Authors: Gornick MC, Castellsague X, Sanchez G, Giordano TJ, Vinco M, Greenson JK, Capella G, Raskin L, Rennert G, Gruber SB, Moreno V
Source: Cancer Causes Control, 2010 May;21(5), p. 737-43.
EPub date: 2010 Jan 20.
PMID: 20087645
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Case-control studies of gene-environment interaction: Bayesian design and analysis.
Authors: Mukherjee B, Ahn J, Gruber SB, Ghosh M, Chatterjee N
Source: Biometrics, 2010 Sep;66(3), p. 934-48.
PMID: 19930190
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Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome.
Authors: Stoffel E, Mukherjee B, Raymond VM, Tayob N, Kastrinos F, Sparr J, Wang F, Bandipalliam P, Syngal S, Gruber SB
Source: Gastroenterology, 2009 Nov;137(5), p. 1621-7.
EPub date: 2009 Jul 18.
PMID: 19622357
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Smoking attenuates the negative association between carotenoids consumption and colorectal cancer risk.
Authors: Chaiter Y, Gruber SB, Ben-Amotz A, Almog R, Rennert HS, Fischler R, Rozen G, Rennert G
Source: Cancer Causes Control, 2009 Oct;20(8), p. 1327-38.
EPub date: 2009 Jun 27.
PMID: 19562494
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Pediatric duodenal cancer and biallelic mismatch repair gene mutations.
Authors: Roy S, Raskin L, Raymond VM, Thibodeau SN, Mody RJ, Gruber SB
Source: Pediatr Blood Cancer, 2009 Jul;53(1), p. 116-20.
PMID: 19283792
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Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk.
Authors: Khoury-Shakour S, Gruber SB, Lejbkowicz F, Rennert HS, Raskin L, Pinchev M, Rennert G
Source: Cancer Epidemiol Biomarkers Prev, 2008 Dec;17(12), p. 3314-8.
PMID: 19064544
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PTPRJ haplotypes and colorectal cancer risk.
Authors: Toland AE, Rozek LS, Presswala S, Rennert G, Gruber SB
Source: Cancer Epidemiol Biomarkers Prev, 2008 Oct;17(10), p. 2782-5.
PMID: 18843023
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Pathologic predictors of microsatellite instability in colorectal cancer.
Authors: Greenson JK, Huang SC, Herron C, Moreno V, Bonner JD, Tomsho LP, Ben-Izhak O, Cohen HI, Trougouboff P, Bejhar J, Sova Y, Pinchev M, Rennert G, Gruber SB
Source: Am J Surg Pathol, 2009 Jan;33(1), p. 126-33.
PMID: 18830122
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Tests for gene-environment interaction from case-control data: a novel study of type I error, power and designs.
Authors: Mukherjee B, Ahn J, Gruber SB, Rennert G, Moreno V, Chatterjee N
Source: Genet Epidemiol, 2008 Nov;32(7), p. 615-26.
PMID: 18473390
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Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.
Authors: Tenesa A, Farrington SM, Prendergast JG, Porteous ME, Walker M, Haq N, Barnetson RA, Theodoratou E, Cetnarskyj R, Cartwright N, Semple C, Clark AJ, Reid FJ, Smith LA, Kavoussanakis K, Koessler T, Pharoah PD, Buch S, Schafmayer C, Tepel J, Schreiber S, Völzke H, Schmidt CO, Hampe J, Chang-Claude J, Hoffmeister M, Brenner H, Wilkening S, Canzian F, Capella G, Moreno V, Deary IJ, Starr JM, Tomlinson IP, Kemp Z, Howarth K, Carvajal-Carmona L, Webb E, Broderick P, Vijayakrishnan J, Houlston RS, Rennert G, Ballinger D, Rozek L, Gruber SB, Matsuda K, Kidokoro T, Nakamura Y, Zanke BW, Greenwood CM, Rangrej J, Kustra R, Montpetit A, Hudson TJ, Gallinger S, Campbell H, Dunlop MG
Source: Nat Genet, 2008 May;40(5), p. 631-7.
EPub date: 2008 Mar 30.
PMID: 18372901
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Genetic variation in 8q24 associated with risk of colorectal cancer.
Authors: Gruber SB, Moreno V, Rozek LS, Rennerts HS, Lejbkowicz F, Bonner JD, Greenson JK, Giordano TJ, Fearson ER, Rennert G
Source: Cancer Biol Ther, 2007 Jul;6(7), p. 1143-7.
PMID: 17630503
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APC I1307K and the risk of prostate cancer.
Authors: Poynter JN, Cooney KA, Bonner JD, White KA, Tomsho LP, Rennert G, Gruber SB
Source: Cancer Epidemiol Biomarkers Prev, 2006 Mar;15(3), p. 468-73.
PMID: 16537703
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New developments in Lynch syndrome (hereditary nonpolyposis colorectal cancer) and mismatch repair gene testing.
Authors: Gruber SB
Source: Gastroenterology, 2006 Feb;130(2), p. 577-87.
PMID: 16472609
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History and molecular genetics of Lynch syndrome in family G: a century later.
Authors: Douglas JA, Gruber SB, Meister KA, Bonner J, Watson P, Krush AJ, Lynch HT
Source: JAMA, 2005 Nov 2;294(17), p. 2195-202.
PMID: 16264161
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Low allele frequency of MLH1 D132H in American colorectal and endometrial cancer patients.
Authors: Shin BY, Chen H, Rozek LS, Paxton L, Peel DJ, Anton-Culver H, Rennert G, Mutch DG, Goodfellow PJ, Gruber SB, Lipkin SM
Source: Dis Colon Rectum, 2005 Sep;48(9), p. 1723-7.
PMID: 15991064
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EGF gene polymorphism and the risk of incident primary melanoma.
Authors: Amend KL, Elder JT, Tomsho LP, Bonner JD, Johnson TM, Schwartz J, Berwick M, Gruber SB
Source: Cancer Res, 2004 Apr 15;64(8), p. 2668-72.
PMID: 15087376
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BRCA1 and BRCA2 founder mutations and the risk of colorectal cancer.
Authors: Niell BL, Rennert G, Bonner JD, Almog R, Tomsho LP, Gruber SB
Source: J Natl Cancer Inst, 2004 Jan 7;96(1), p. 15-21.
PMID: 14709734
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Genetic anthropology of the colorectal cancer-susceptibility allele APC I1307K: evidence of genetic drift within the Ashkenazim.
Authors: Niell BL, Long JC, Rennert G, Gruber SB
Source: Am J Hum Genet, 2003 Dec;73(6), p. 1250-60.
EPub date: 2003 Nov 17.
PMID: 14624392
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Phenotype of microsatellite unstable colorectal carcinomas: Well-differentiated and focally mucinous tumors and the absence of dirty necrosis correlate with microsatellite instability.
Authors: Greenson JK, Bonner JD, Ben-Yzhak O, Cohen HI, Miselevich I, Resnick MB, Trougouboff P, Tomsho LD, Kim E, Low M, Almog R, Rennert G, Gruber SB
Source: Am J Surg Pathol, 2003 May;27(5), p. 563-70.
PMID: 12717242
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R726L androgen receptor mutation is uncommon in prostate cancer families in the united states.
Authors: Gruber SB, Chen H, Tomsho LP, Lee N, Perrone EE, Cooney KA
Source: Prostate, 2003 Mar 1;54(4), p. 306-9.
PMID: 12539229
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The founder mutation MSH2*1906G-->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population.
Authors: Foulkes WD, Thiffault I, Gruber SB, Horwitz M, Hamel N, Lee C, Shia J, Markowitz A, Figer A, Friedman E, Farber D, Greenwood CM, Bonner JD, Nafa K, Walsh T, Marcus V, Tomsho L, Gebert J, Macrae FA, Gaff CL, Paillerets BB, Gregersen PK, Weitzel JN, Gordon PH, MacNamara E, King MC, Hampel H, De La Chapelle A, Boyd J, Offit K, Rennert G, Chong G, Ellis NA
Source: Am J Hum Genet, 2002 Dec;71(6), p. 1395-412.
EPub date: 2002 Nov 26.
PMID: 12454801
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Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles.
Authors: Giordano TJ, Shedden KA, Schwartz DR, Kuick R, Taylor JM, Lee N, Misek DE, Greenson JK, Kardia SL, Beer DG, Rennert G, Cho KR, Gruber SB, Fearon ER, Hanash S
Source: Am J Pathol, 2001 Oct;159(4), p. 1231-8.
PMID: 11583950
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Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies.
Authors: Douglas JA, Boehnke M, Gillanders E, Trent JM, Gruber SB
Source: Nat Genet, 2001 Aug;28(4), p. 361-4.
PMID: 11443299
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