Grant Number:	5R01CA107028-04 Interpret this number
Primary Investigator:	Luebeck, E
Organization:	Fred Hutchinson Cancer Research Center
Project Title:	Modeling Colon Cancer, Intervention and Prevention
Fiscal Year:	2008

DESCRIPTION (provided by applicant): Mathematical models of carcinogenesis that are designed to capture important features of the multistage process, from normal cells, via expanding intermediate cell populations, to the appearance of malignant tumors, offer the opportunity to study in greater detail the effects of specific interventions that affect critical biological processes involved in carcinogenesis. The main focus of this proposal is therefore the development of tools and methods for the quantitative evaluation of possible prevention and intervention strategies and to apply them to colorectal cancer. These tools and methods will be based on stochastic models of carcinogenesis that reflect insights gained into the pathogenesis of colon cancer over the past decade, as well as extensions of these models that allow for the incorporation of additional (putative) pathways associated with genomic instability. To achieve this goal with confidence, it is important that the models used for this purpose give satisfactory descriptions of the incidence of colon cancer in the general population. A challenge, so far unmet, is that these models also be consistent with observations on the prevalence and size distribution of adenomatous polyps, pathologically well-characterized precursor lesions to colorectal tumors. These polyps are also the subject of specific cancer screening and intervention strategies. This motivates the mathematical development of statistical and computational tools to analyze relevant data sets: (1) the SEER registry data on colorectal cancer (CRC) incidence, (2) CRC incidence in a large prospective cohort of women (the Shanghai study), (3) the Minnesota Cancer Prevention Research Unit (CPRU) polyp data, and (4) data from a case-control study of CRC and the role of sigmoidoscopy conducted at the Fred Hutchinson Cancer Research Center. Models derived from these analyses and the computational tools developed will facilitate the prediction of benefits associated with specific screening, prevention and intervention strategies.




Incremental Benefits Of Screening Colonoscopy Over Sigmoidoscopy In Average-risk Populations: A Model-driven Analysis
Authors: Jeon J. , Meza R. , Hazelton W.D. , Renehan A.G. , Luebeck E.G. .
Source: Cancer Causes & Control : Ccc, 2015 Jun; 26(6), p. 859-70.
PMID: 25783458
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Impact of tumor progression on cancer incidence curves.
Authors: Luebeck E.G. , Curtius K. , Jeon J. , Hazelton W.D. .
Source: Cancer Research, 2013-02-01 00:00:00.0; 73(3), p. 1086-96.
EPub date: 2013-02-01 00:00:00.0.
PMID: 23054397
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Longitudinal multistage model for lung cancer incidence, mortality, and CT detected indolent and aggressive cancers.
Authors: Hazelton W.D. , Goodman G. , Rom W.N. , Tockman M. , Thornquist M. , Moolgavkar S. , Weissfeld J.L. , Feng Z. .
Source: Mathematical Biosciences, 2012 Nov; 240(1), p. 20-34.
PMID: 22705252
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Development and characterization of an organotypic model of Barrett's esophagus.
Authors: Kosoff R.E. , Gardiner K.L. , Merlo L.M. , Pavlov K. , Rustgi A.K. , Maley C.C. .
Source: Journal Of Cellular Physiology, 2012 Jun; 227(6), p. 2654-9.
PMID: 21882191
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Biomarker-based early cancer detection: is it achievable?
Authors: Hazelton W.D. , Luebeck E.G. .
Source: Science Translational Medicine, 2011-11-16 00:00:00.0; 3(109), p. 109fs9.
PMID: 22089449
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Number And Size Distribution Of Colorectal Adenomas Under The Multistage Clonal Expansion Model Of Cancer
Authors: Dewanji A. , Jeon J. , Meza R. , Luebeck E.G. .
Source: Plos Computational Biology, 2011 Oct; 7(10), p. e1002213.
PMID: 22022253
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A comprehensive survey of clonal diversity measures in Barrett's esophagus as biomarkers of progression to esophageal adenocarcinoma.
Authors: Merlo L.M. , Shah N.A. , Li X. , Blount P.L. , Vaughan T.L. , Reid B.J. , Maley C.C. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2010 Nov; 3(11), p. 1388-97.
PMID: 20947487
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Multiscale Estimation Of Cell Kinetics
Authors: Jean L.W. , Suchorolski M.T. , Jeon J. , Luebeck E.G. .
Source: Computational And Mathematical Methods In Medicine, 2010 Sep; 11(3), p. 239-54.
PMID: 20582763
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Colorectal Cancer Incidence Trends In The United States And United Kingdom: Evidence Of Right- To Left-sided Biological Gradients With Implications For Screening
Authors: Meza R. , Jeon J. , Renehan A.G. , Luebeck E.G. .
Source: Cancer Research, 2010-07-01 00:00:00.0; 70(13), p. 5419-29.
PMID: 20530677
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Age-specific Incidence Of Cancer: Phases, Transitions, And Biological Implications
Authors: Meza R. , Jeon J. , Moolgavkar S.H. , Luebeck E.G. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008-10-21 00:00:00.0; 105(42), p. 16284-9.
PMID: 18936480
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Does Folic Acid Supplementation Prevent Or Promote Colorectal Cancer? Results From Model-based Predictions
Authors: Luebeck E.G. , Moolgavkar S.H. , Liu A.Y. , Boynton A. , Ulrich C.M. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2008 Jun; 17(6), p. 1360-7.
PMID: 18539928
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Evaluation Of Screening Strategies For Pre-malignant Lesions Using A Biomathematical Approach
Authors: Jeon J. , Meza R. , Moolgavkar S.H. , Luebeck E.G. .
Source: Mathematical Biosciences, 2008 May; 213(1), p. 56-70.
PMID: 18374369
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