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Principal Investigator: Scott D. Ramsey
Institution:
Fred Hutchinson Cancer Research Center
Grant Number: 5R01CA114794-02
Abstract: As our knowledge of the role of genetic and environmental
factors in colorectal cancer grows, population screening and prevention efforts can be modified
to incorporate this information. The goal of this study is to develop a framework for evaluating
the clinical and economic tradeoffs that occur when considering gene-based strategies directed
towards identifying persons at increased risk for colon cancer. We propose to extend an existing
model of colorectal cancer progression, screening and diagnosis to incorporate genetic variation
in the population, and the impact of common genetic polymorphisms and haplotypes on disease
progression and incidence. The model will be used to project the cost-effectiveness of a
variety of genetic testing and colorectal cancer screening strategies. We propose to inform
the model using data from a unique and valuable resource - the Colorectal Cancer Family Registry
- Seattle (Seattle CFR). The specific aims are as follows: (1) (1a) Develop a model of genetic
testing for common polymorphisms and haplotypes associated with CRC risk, by extending a
state-of-the-art microsimulation model of colorectal cancer progression, screening and diagnosis
(MISCAN-Colon). The extended model will include clinical and epidemiologic information related
to genetic variants and will model their impact on colorectal cancer progression and incidence.
(1b) Validate the model by comparing results generated from the model with polymorphism/haplotype
frequencies among CRC cases and controls in the Seattle CFR. (2) Survey individuals enrolled
in the Seattle CFR to estimate quality-of-life (QOL) effects related to polymorphism and
haplotype screening, specifically considering individuals' personal and family history of
colorectal cancer at the time of testing and how this influences the QOL impact of learning
that one is a polymorphism carrier. Hypothesis: QOL for those with the polymorphism/haplotype
state associated with increased CRC risk will be reduced, compared to those without the variant
and those whose genetic status is unknown. (3) Using the model, simulate a variety of genetic
testing and CRC screening approaches to estimate the cost effectiveness of alternative strategies
of population testing for polymorphisms and haplotypes linked to colorectal cancer. The model
will incorporate QOL information from Aim 2, along with family history, clinical, and screening
information from the Seattle CFR.
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