Grant Number:	5R01CA097325-06 Interpret this number
Primary Investigator:	Newcomb, Polly
Organization:	Fred Hutchinson Cancer Research Center
Project Title:	Colon Cancer Pathways: Hyperplastic Polyps and Adenomas
Fiscal Year:	2009

DESCRIPTION (provided by applicant): According to current clinical practice guidelines, hyperplastic polyps are benign lesions that can be safely ignored. However, recent evidence suggests that hyperplastic polyps, a common finding in nearly 30% of adults, may indeed be pre-neoplastic lesions. While only a minority of hyperplastic polyps progress to malignancy, the characteristics of those at-risk lesions are not fully known. In molecular terms, the presence of microsatellite instability (MSI) and/or CpG island methylation (CIMP) may be the hallmark of hyperplastic polyps that give rise to sporadic colorectal carcinomas. In this emerging paradigm, there is a great need to confirm these findings on a well-characterized sample, and more importantly, to understand the environmental and genetic characteristics that are associated with hyperplastic polyps, particularly in comparison to the better understood adenomas. To investigate the relationship between risk factors, epigenetic characteristics, and polyps, we propose to conduct a population based case-control study of hyperplastic polyps, adenomatous polyps, and normal controls. Individuals with a new diagnosis of polyps (hyperplastic polyps n=700, adenomas n=700) will be identified by a centralized review of the pathology files of Group Health Cooperative (GHC) of Puget Sound a large health maintenance organization. Similarly aged individuals with normal screening colonoscopies (n=700) will be identified from procedure files. All subjects will complete a standardized interview and provide a buccal sample. The diagnostic materials of all cases will be reviewed, DNA extracted from lesional blocks, and MSI and CIMP status will be assessed using standard panels of markers. Polymorphisms in epoxide hydrolase (mEH), which are involved in the detoxification of polyaromatic hydrocarbons in smoke and cooked meat, will be evaluated for their modifying effect on environmental exposures. This study will provide the largest study of risk factors for hyperplastic polyps, their genetic characterization, and comparisons to adenomas and normals. In this study neoplastic pathways will be classified on the basis of genetic instability, DNA methylation phenotype, and epidemiologic risk factors. The results of this study will have implications for understanding the biology and prevention of colorectal cancer.




Circulating Levels of Testosterone, Sex Hormone Binding Globulin and Colorectal Cancer Risk: Observational and Mendelian Randomization Analyses.
Authors: Dimou N. , Mori N. , Harlid S. , Harbs J. , Martin R.M. , Smith-Byrne K. , Papadimitriou N. , Bishop D.T. , Casey G. , Colorado-Yohar S.M. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2021 07; 30(7), p. 1336-1348.
EPub date: 2021-04-20.
PMID: 33879453
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Causal Effects of Lifetime Smoking on Breast and Colorectal Cancer Risk: Mendelian Randomization Study.
Authors: Dimou N. , Yarmolinsky J. , Bouras E. , Tsilidis K.K. , Martin R.M. , Lewis S.J. , Gram I.T. , Bakker M.F. , Brenner H. , Figueiredo J.C. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2021 05; 30(5), p. 953-964.
EPub date: 2021-03-02.
PMID: 33653810
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Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study.
Authors: Dimou N.L. , Papadimitriou N. , Mariosa D. , Johansson M. , Brennan P. , Peters U. , Chanock S.J. , Purdue M. , Bishop D.T. , Gago-Dominquez M. , et al. .
Source: International journal of cancer, 2021-04-01; 148(7), p. 1625-1636.
EPub date: 2020-10-26.
PMID: 33038280
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A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer.
Authors: Nounu A. , Greenhough A. , Heesom K.J. , Richmond R.C. , Zheng J. , Weinstein S.J. , Albanes D. , Baron J.A. , Hopper J.L. , Figueiredo J.C. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2021 03; 30(3), p. 564-575.
EPub date: 2020-12-14.
PMID: 33318029
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Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.
Authors: Guo X. , Lin W. , Wen W. , Huyghe J. , Bien S. , Cai Q. , Harrison T. , Chen Z. , Qu C. , Bao J. , et al. .
Source: Gastroenterology, 2021 03; 160(4), p. 1164-1178.e6.
EPub date: 2020-10-12.
PMID: 33058866
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Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study.
Authors: Bull C.J. , Bell J.A. , Murphy N. , Sanderson E. , Davey Smith G. , Timpson N.J. , Banbury B.L. , Albanes D. , Berndt S.I. , Bézieau S. , et al. .
Source: BMC medicine, 2020-12-17; 18(1), p. 396.
EPub date: 2020-12-17.
PMID: 33327948
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Associations between molecular characteristics of colorectal serrated polyps and subsequent advanced colorectal neoplasia.
Authors: Hua X. , Newcomb P.A. , Chubak J. , Malen R.C. , Ziebell R. , Kamineni A. , Zhu L.C. , Upton M.P. , Wurscher M.A. , Thomas S.S. , et al. .
Source: Cancer causes & control : CCC, 2020 Jul; 31(7), p. 631-640.
EPub date: 2020-05-01.
PMID: 32358694
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Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses.
Authors: Murphy N. , Carreras-Torres R. , Song M. , Chan A.T. , Martin R.M. , Papadimitriou N. , Dimou N. , Tsilidis K.K. , Banbury B. , Bradbury K.E. , et al. .
Source: Gastroenterology, 2020 04; 158(5), p. 1300-1312.e20.
EPub date: 2019-12-27.
PMID: 31884074
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Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians.
Authors: Lu Y. , Kweon S.S. , Cai Q. , Tanikawa C. , Shu X.O. , Jia W.H. , Xiang Y.B. , Huyghe J.R. , Harrison T.A. , Kim J. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2020 02; 29(2), p. 477-486.
EPub date: 2019-12-11.
PMID: 31826910
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The association between colorectal sessile serrated adenomas/polyps and subsequent advanced colorectal neoplasia.
Authors: Burnett-Hartman A.N. , Chubak J. , Hua X. , Ziebell R. , Kamineni A. , Zhu L.C. , Upton M.P. , Malen R.C. , Hardikar S. , Newcomb P.A. .
Source: Cancer causes & control : CCC, 2019 Sep; 30(9), p. 979-987.
EPub date: 2019-07-09.
PMID: 31290073
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Telomere length differences between colorectal polyp subtypes: a colonoscopy-based case-control study.
Authors: Hardikar S. , Burnett-Hartman A.N. , Phipps A.I. , Upton M.P. , Zhu L.C. , Newcomb P.A. .
Source: BMC cancer, 2018-05-02; 18(1), p. 513.
EPub date: 2018-05-02.
PMID: 29720120
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Reproductive factors and risk of colorectal polyps in a colonoscopy-based study in western Washington State.
Authors: Hardikar S. , Burnett-Hartman A.N. , Chubak J. , Upton M.P. , Zhu L.C. , Potter J.D. , Newcomb P.A. .
Source: Cancer causes & control : CCC, 2017 03; 28(3), p. 241-246.
EPub date: 2017-02-15.
PMID: 28205046
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Blood Lipid Concentrations and Colorectal Adenomas: A Systematic Review and Meta-Analysis of Colonoscopy Studies in Asia, 2000-2014.
Authors: Passarelli M.N. , Newcomb P.A. .
Source: American journal of epidemiology, 2016-04-15; 183(8), p. 691-700.
EPub date: 2016-03-24.
PMID: 27013025
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Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization.
Authors: Passarelli M.N. , Newcomb P.A. , Makar K.W. , Burnett-Hartman A.N. , Potter J.D. , Upton M.P. , Zhu L.C. , Rosenfeld M.E. , Schwartz S.M. , Rutter C.M. .
Source: Cancer causes & control : CCC, 2015 Mar; 26(3), p. 467-73.
EPub date: 2015-01-25.
PMID: 25618792
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Variation in the association between colorectal cancer susceptibility loci and colorectal polyps by polyp type.
Authors: Burnett-Hartman A.N. , Newcomb P.A. , Hutter C.M. , Peters U. , Passarelli M.N. , Schwartz M.R. , Upton M.P. , Zhu L.C. , Potter J.D. , Makar K.W. .
Source: American journal of epidemiology, 2014-07-15; 180(2), p. 223-32.
EPub date: 2014-05-29.
PMID: 24875374
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Genomic aberrations occurring in subsets of serrated colorectal lesions but not conventional adenomas.
Authors: Burnett-Hartman A.N. , Newcomb P.A. , Potter J.D. , Passarelli M.N. , Phipps A.I. , Wurscher M.A. , Grady W.M. , Zhu L.C. , Upton M.P. , Makar K.W. .
Source: Cancer research, 2013-05-01; 73(9), p. 2863-72.
EPub date: 2013-03-28.
PMID: 23539450
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Differences in epidemiologic risk factors for colorectal adenomas and serrated polyps by lesion severity and anatomical site.
Authors: Burnett-Hartman A.N. , Passarelli M.N. , Adams S.V. , Upton M.P. , Zhu L.C. , Potter J.D. , Newcomb P.A. .
Source: American journal of epidemiology, 2013-04-01; 177(7), p. 625-37.
EPub date: 2013-03-03.
PMID: 23459948
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Authors: Burnett-Hartman A.N. , Newcomb P.A. , Phipps A.I. , Passarelli M.N. , Grady W.M. , Upton M.P. , Zhu L.C. , Potter J.D. .
Source: The American journal of gastroenterology, 2012 Aug; 107(8), p. 1213-9.
EPub date: 2012-06-12.
PMID: 22688851
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Authors: Burnett-Hartman A.N. , Newcomb P.A. , Mandelson M.T. , Adams S.V. , Wernli K.J. , Shadman M. , Wurscher M.A. , Makar K.W. .
Source: Nutrition and cancer, 2011; 63(4), p. 583-92.
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Authors: Wernli K.J. , Newcomb P.A. , Wang Y. , Makar K.W. , Shadman M. , Chia V.M. , Burnett-Hartman A. , Wurscher M.A. , Zheng Y. , Mandelson M.T. .
Source: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 2010 Aug; 20(4), p. 305-9.
EPub date: 2010-05-26.
PMID: 20580999
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Authors: Ceballos R.M. , Newcomb P.A. , Beasley J.M. , Peterson S. , Templeton A. , Hunt J.R. .
Source: Genetic testing, 2008 Sep; 12(3), p. 415-20.
PMID: 18752450
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