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Grant Details

Grant Number: 5U01CA137088-09 Interpret this number
Primary Investigator: Peters, Ulrike
Organization: Fred Hutchinson Cancer Research Center
Project Title: Molecular Pathological Epidemiology of Colorectal Cancer
Fiscal Year: 2018
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Abstract

DESCRIPTION (provided by applicant): Colorectal cancer (CRC), the second most commonly diagnosed cancer, is a biologically heterogeneous disease. Molecular characterization of tumors, including somatic mutations in BRAF and KRAS, microsatellite instability (MSI), and CpG island methylator phenotype (CIMP), has provided evidence of multiple tumor subtypes that develop through activation of diverse neoplastic pathways. More recently, new technologies, such as next-generation sequencing as applied in The Cancer Genome Atlas (TCGA) Project1, have enabled further characterization by identifying mutated genes in colorectal tumors, including well known genes, such as APC, SMAD4, and PIK3CA as well as some that are less well known, such as SOX9 or ACVR1B. These discoveries highlight the importance of a number of key pathways, including MAPK, Wnt, or TGF? signaling pathways. These detailed molecular data now allow us to better define tumor subtypes by mutated genes and pathways. Knowledge of the relationship between etiologic factors for CRC-such as germline genetic, lifestyle, and environmental risk factors- and tumor subtype is critical to improve our understanding of the underlying carcinogenic mechanisms that result in different molecular subtypes of CRC; however, these relations have not been comprehensively studied. To address this, we propose to use existing resources of the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR). These consortia are based on well-characterized cohort and population-based case-control studies and have available extensive germline genetic, clinical, and epidemiologic data. In addition, a large subset of cases has already undergone molecular characterization for BRAF and KRAS mutations, MSI, and CIMP. We will harmonize these existing tumor characteristics in Aim 1 in up to 11,900 CRC cases to investigate associations between defined CRC subtypes and a) common and rare germline genetic variants across the genome (Aim 1a), as well as b) lifestyle and environmental risk factors, such as alcohol, smoking, obesity, hormone use, or dietary factors (Aim 1b). In Aim 2 we will use the tumor DNA of 4,200 CRC cases by deeply sequencing approximately 100 genes identified through existing and ongoing CRC tumor tissue sequencing studies (e.g., TCGA) to define new CRC subtypes based on mutated pathways, such as Wnt, PI3K, or TGF? signaling. We will investigate associations between these subtypes and common and rare germline genetic variants across the genome (Aim 2a), as well as lifestyle and environmental risk factors (Aim 2b). This integrated approach addresses important gaps in knowledge about the risk-factor profile of existing and newly-defined molecular subtypes of CRC. Our large and well characterized study population provides a unique opportunity to define new molecular classifications with improved precision. This precision is needed to better understand how genetic and environmental risk factors, together, contribute to individual risk of CRC. These insights on carcinogenic mechanisms can help optimize prevention measures and will have an important public health impact.

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Publications

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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Relationship of prediagnostic body mass index with survival after colorectal cancer: Stage-specific associations.
Authors: Kocarnik J.M. , Chan A.T. , Slattery M.L. , Potter J.D. , Meyerhardt J. , Phipps A. , Nan H. , Harrison T. , Rohan T.E. , Qi L. , et al. .
Source: International Journal Of Cancer, 2016-09-01 00:00:00.0; 139(5), p. 1065-72.
EPub date: 2016-09-01 00:00:00.0.
PMID: 27121247
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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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The Effect Of Phenotypic Outliers And Non-normality On Rare-variant Association Testing
Authors: Auer P.L. , Reiner A.P. , Leal S.M. .
Source: European Journal Of Human Genetics : Ejhg, 2016 Aug; 24(8), p. 1188-94.
PMID: 26733287
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Meta-analysis Of Rare And Common Exome Chip Variants Identifies S1pr4 And Other Loci Influencing Blood Cell Traits
Authors: CHARGE Consortium Hematology Working Group .
Source: Nature Genetics, 2016 Aug; 48(8), p. 867-76.
PMID: 27399967
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A Unified Powerful Set-based Test For Sequencing Data Analysis Of Gxe Interactions
Authors: Su Y.R. , Di C.Z. , Hsu L. , Genetics and Epidemiology of Colorectal Cancer Consortium .
Source: Biostatistics (oxford, England), 2016-07-28 00:00:00.0; , .
PMID: 27474101
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Snps In Transporter And Metabolizing Genes As Predictive Markers For Oxaliplatin Treatment In Colorectal Cancer Patients
Authors: Kap E.J. , Seibold P. , Scherer D. , Habermann N. , Balavarca Y. , Jansen L. , Zucknick M. , Becker N. , Hoffmeister M. , Ulrich A. , et al. .
Source: International Journal Of Cancer, 2016-06-15 00:00:00.0; 138(12), p. 2993-3001.
PMID: 26835885
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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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A Genome-wide Investigation Of Food Addiction
Authors: Cornelis M.C. , Flint A. , Field A.E. , Kraft P. , Han J. , Rimm E.B. , van Dam R.M. .
Source: Obesity (silver Spring, Md.), 2016 Jun; 24(6), p. 1336-41.
PMID: 27106561
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Cyp24a1 Variant Modifies The Association Between Use Of Oestrogen Plus Progestogen Therapy And Colorectal Cancer Risk
Authors: Garcia-Albeniz X. , Rudolph A. , Hutter C. , White E. , Lin Y. , Rosse S.A. , Figueiredo J.C. , Harrison T.A. , Jiao S. , Brenner H. , et al. .
Source: British Journal Of Cancer, 2016-01-19 00:00:00.0; 114(2), p. 221-9.
PMID: 26766742
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A Meta-analysis Of 120 246 Individuals Identifies 18 New Loci For Fibrinogen Concentration
Authors: de Vries P.S. , Chasman D.I. , Sabater-Lleal M. , Chen M.H. , Huffman J.E. , Steri M. , Tang W. , Teumer A. , Marioni R.E. , Grossmann V. , et al. .
Source: Human Molecular Genetics, 2016-01-15 00:00:00.0; 25(2), p. 358-70.
PMID: 26561523
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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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Powerful Set-Based Gene-Environment Interaction Testing Framework for Complex Diseases.
Authors: Jiao S. , Peters U. , Berndt S. , Bézieau S. , Brenner H. , Campbell P.T. , Chan A.T. , Chang-Claude J. , Lemire M. , Newcomb P.A. , et al. .
Source: Genetic Epidemiology, 2015 Dec; 39(8), p. 609-18.
PMID: 26095235
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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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A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1.
Authors: Lemire M. , Qu C. , Loo L.W. , Zaidi S.H. , Wang H. , Berndt S.I. , Bézieau S. , Brenner H. , Campbell P.T. , Chan A.T. , et al. .
Source: Human Genetics, 2015 Nov; 134(11-12), p. 1249-62.
PMID: 26404086
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Genetic architecture of colorectal cancer.
Authors: Peters U. , Bien S. , Zubair N. .
Source: Gut, 2015 Oct; 64(10), p. 1623-36.
PMID: 26187503
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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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Identification of a common variant with potential pleiotropic effect on risk of inflammatory bowel disease and colorectal cancer.
Authors: Khalili H. , Gong J. , Brenner H. , Austin T.R. , Hutter C.M. , Baba Y. , Baron J.A. , Berndt S.I. , Bézieau S. , Caan B. , et al. .
Source: Carcinogenesis, 2015 Sep; 36(9), p. 999-1007.
PMID: 26071399
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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 reference panel of 64,976 haplotypes for genotype imputation.
Authors: McCarthy S. , Das S. , Kretzschmar W. , Delaneau O. , Wood A.R. , Teumer A. , Kang H.M. , Fuchsberger C. , Danecek P. , Sharp K. , et al. .
Source: Nature Genetics, 2016 10; 48(10), p. 1279-83.
EPub date: 2016-08-22 00:00:00.0.
PMID: 27548312
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Association Between Intake of Red and Processed Meat and Survival in Patients With Colorectal Cancer in a Pooled Analysis.
Authors: Carr P.R. , Banbury B. , Berndt S.I. , Campbell P.T. , Chang-Claude J. , Hayes R.B. , Howard B.V. , Jansen L. , Jacobs E. , Lane D.S. , et al. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2018-11-23 00:00:00.0; , .
EPub date: 2018-11-23 00:00:00.0.
PMID: 30476588
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Healthy Lifestyle Factors Associated With Lower Risk of Colorectal Cancer Irrespective of Genetic Risk.
Authors: Carr P.R. , Weigl K. , Jansen L. , Walter V. , Erben V. , Chang-Claude J. , Brenner H. , Hoffmeister M. .
Source: Gastroenterology, 2018-09-07 00:00:00.0; , .
EPub date: 2018-09-07 00:00:00.0.
PMID: 30201362
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Influence of smoking, body mass index and other factors on the preventive effect of nonsteroidal anti-inflammatory drugs on colorectal cancer risk.
Authors: Wang X. , Chan A.T. , Slattery M.L. , Chang-Claude J. , Potter J.D. , Gallinger S. , Caan B. , Lampe J.W. , Newcomb P.A. , Zubair N. , et al. .
Source: Cancer Research, 2018-06-19 00:00:00.0; , .
EPub date: 2018-06-19 00:00:00.0.
PMID: 29921691
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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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A Mixed-Effects Model for Powerful Association Tests in Integrative Functional Genomics.
Authors: Su Y.R. , Di C. , Bien S. , Huang L. , Dong X. , Abecasis G. , Berndt S. , Bezieau S. , Brenner H. , Caan B. , et al. .
Source: American Journal Of Human Genetics, 2018-05-03 00:00:00.0; 102(5), p. 904-919.
PMID: 29727690
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Genetic mechanisms of immune evasion in colorectal cancer.
Authors: Grasso C.S. , Giannakis M. , Wells D.K. , Hamada T. , Mu X.J. , Quist M. , Nowak J.A. , Nishihara R. , Qian Z.R. , Inamura K. , et al. .
Source: Cancer Discovery, 2018-03-06 00:00:00.0; , .
EPub date: 2018-03-06 00:00:00.0.
PMID: 29510987
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Multivariate association analysis with somatic mutation data.
Authors: He Q. , Liu Y. , Peters U. , Hsu L. .
Source: Biometrics, 2018 Mar; 74(1), p. 176-184.
EPub date: 2017-07-19 00:00:00.0.
PMID: 28722765
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Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors.
Authors: Jeon J. , Du M. , Schoen R.E. , Hoffmeister M. , Newcomb P.A. , Berndt S.I. , Caan B. , Campbell P.T. , Chan A.T. , Chang-Claude J. , et al. .
Source: Gastroenterology, 2018-02-16 00:00:00.0; , .
EPub date: 2018-02-16 00:00:00.0.
PMID: 29458155
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Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine.
Authors: Ogino S. , Nowak J.A. , Hamada T. , Phipps A.I. , Peters U. , Milner D.A. , Giovannucci E.L. , Nishihara R. , Giannakis M. , Garrett W.S. , et al. .
Source: Gut, 2018-02-06 00:00:00.0; , .
EPub date: 2018-02-06 00:00:00.0.
PMID: 29437869
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Strongly enhanced colorectal cancer risk stratification by combining family history and genetic risk score.
Authors: Weigl K. , Chang-Claude J. , Knebel P. , Hsu L. , Hoffmeister M. , Brenner H. .
Source: Clinical Epidemiology, 2018; 10, p. 143-152.
EPub date: 2018-01-19 00:00:00.0.
PMID: 29403313
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Genetic susceptibility markers for a breast-colorectal cancer phenotype: Exploratory results from genome-wide association studies.
Authors: Pande M. , Joon A. , Brewster A.M. , Chen W.V. , Hopper J.L. , Eng C. , Shete S. , Casey G. , Schumacher F. , Lin Y. , et al. .
Source: Plos One, 2018; 13(4), p. e0196245.
EPub date: 2018-04-26 00:00:00.0.
PMID: 29698419
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GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.
Authors: Pirastu N. , Joshi P.K. , de Vries P.S. , Cornelis M.C. , McKeigue P.M. , Keum N. , Franceschini N. , Colombo M. , Giovannucci E.L. , Spiliopoulou A. , et al. .
Source: Nature Communications, 2017-11-17 00:00:00.0; 8(1), p. 1584.
EPub date: 2017-11-17 00:00:00.0.
PMID: 29146897
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Genome-wide association study of heart rate and its variability in Hispanic/Latino cohorts.
Authors: Kerr K.F. , Avery C.L. , Lin H.J. , Raffield L.M. , Zhang Q.S. , Browning B.L. , Browning S.R. , Conomos M.P. , Gogarten S.M. , Laurie C.C. , et al. .
Source: Heart Rhythm, 2017 Nov; 14(11), p. 1675-1684.
EPub date: 2017-06-10 00:00:00.0.
PMID: 28610988
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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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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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On Estimation Of Time-dependent Attributable Fraction From Population-based Case-control Studies
Authors: Zhao W. , Chen Y.Q. , Hsu L. .
Source: Biometrics, 2017-01-18 00:00:00.0; , .
PMID: 28099992
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Enrichment of colorectal cancer associations in functional regions: Insight for using epigenomics data in the analysis of whole genome sequence-imputed GWAS data.
Authors: Bien S.A. , Auer P.L. , Harrison T.A. , Qu C. , Connolly C.M. , Greenside P.G. , Chen S. , Berndt S.I. , Bézieau S. , Kang H.M. , et al. .
Source: Plos One, 2017; 12(11), p. e0186518.
EPub date: 2017-11-21 00:00:00.0.
PMID: 29161273
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Genetic Variants In Dna Repair Genes As Potential Predictive Markers For Oxaliplatin Chemotherapy In Colorectal Cancer
Authors: Kap E.J. , Seibold P. , Richter S. , Scherer D. , Habermann N. , Balavarca Y. , Jansen L. , Becker N. , Pfütze K. , Popanda O. , et al. .
Source: The Pharmacogenomics Journal, 2015 Dec; 15(6), p. 505-12.
PMID: 25778469
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Dna Methylation Variants At Hif3a Locus, B-vitamin Intake, And Long-term Weight Change: Gene-diet Interactions In Two U.s. Cohorts
Authors: Huang T. , Zheng Y. , Qi Q. , Xu M. , Ley S.H. , Li Y. , Kang J.H. , Wiggs J. , Pasquale L.R. , Chan A.T. , et al. .
Source: Diabetes, 2015 Sep; 64(9), p. 3146-54.
PMID: 26001398
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Analyses Of 7,635 Patients With Colorectal Cancer Using Independent Training And Validation Cohorts Show That Rs9929218 In Cdh1 Is A Prognostic Marker Of Survival
Authors: Smith C.G. , Fisher D. , Harris R. , Maughan T.S. , Phipps A.I. , Richman S. , Seymour M. , Tomlinson I. , Rosmarin D. , Kerr D. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2015-08-01 00:00:00.0; 21(15), p. 3453-61.
PMID: 25873087
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Genetic variants of adiponectin and risk of colorectal cancer.
Authors: Song M. , Gong J. , Giovannucci E.L. , Berndt S.I. , Brenner H. , Chang-Claude J. , Curtis K.R. , Harrison T.A. , Hoffmeister M. , Hsu L. , et al. .
Source: International Journal Of Cancer, 2015-07-01 00:00:00.0; 137(1), p. 154-64.
EPub date: 2015-07-01 00:00:00.0.
PMID: 25431318
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Genetic Predisposition to Central Obesity and Risk of Type 2 Diabetes: Two Independent Cohort Studies.
Authors: Huang T. , Qi Q. , Zheng Y. , Ley S.H. , Manson J.E. , Hu F.B. , Qi L. .
Source: Diabetes Care, 2015 Jul; 38(7), p. 1306-11.
PMID: 25852209
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Mendelian Randomization Study Of Body Mass Index And Colorectal Cancer Risk
Authors: Thrift A.P. , Gong J. , Peters U. , Chang-Claude J. , Rudolph A. , Slattery M.L. , Chan A.T. , Locke A.E. , Kahali B. , Justice A.E. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Jul; 24(7), p. 1024-31.
PMID: 25976416
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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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Is The Adiposity-associated Fto Gene Variant Related To All-cause Mortality Independent Of Adiposity? Meta-analysis Of Data From 169,551 Caucasian Adults
Authors: Zimmermann E. , Ängquist L.H. , Mirza S.S. , Zhao J.H. , Chasman D.I. , Fischer K. , Qi Q. , Smith A.V. , Thinggaard M. , Jarczok M.N. , et al. .
Source: Obesity Reviews : An Official Journal Of The International Association For The Study Of Obesity, 2015 Apr; 16(4), p. 327-40.
PMID: 25752329
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Mendelian Randomization Study Of Height And Risk Of Colorectal Cancer
Authors: Thrift A.P. , Gong J. , Peters U. , Chang-Claude J. , Rudolph A. , Slattery M.L. , Chan A.T. , Esko T. , Wood A.R. , Yang J. , et al. .
Source: International Journal Of Epidemiology, 2015 Apr; 44(2), p. 662-72.
PMID: 25997436
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Association Of Aspirin And Nsaid Use With Risk Of Colorectal Cancer According To Genetic Variants
Authors: Nan H. , Hutter C.M. , Lin Y. , Jacobs E.J. , Ulrich C.M. , White E. , Baron J.A. , Berndt S.I. , Brenner H. , Butterbach K. , et al. .
Source: Jama, 2015-03-17 00:00:00.0; 313(11), p. 1133-42.
PMID: 25781442
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Red Meat Intake, Nat2, And Risk Of Colorectal Cancer: A Pooled Analysis Of 11 Studies
Authors: Ananthakrishnan A.N. , Du M. , Berndt S.I. , Brenner H. , Caan B.J. , Casey G. , Chang-Claude J. , Duggan D. , Fuchs C.S. , Gallinger 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, 2015 Jan; 24(1), p. 198-205.
PMID: 25342387
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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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Gene-environment interaction involving recently identified colorectal cancer susceptibility Loci.
Authors: Kantor E.D. , Hutter C.M. , Minnier J. , Berndt S.I. , Brenner H. , Caan B.J. , Campbell P.T. , 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 Sep; 23(9), p. 1824-33.
PMID: 24994789
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