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Published on: September 19, 2019
Stochastic dynamics of cancer initiation
Jasmine Foo1, Kevin Leder, Franziska Michor
1Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Physical Biology
|February 9, 2011
Summary
This study introduces a mathematical model for cancer initiation, exploring how genetic changes and aging interact. It reveals how mutation fitness and life expectancy influence cancer development over a lifetime.
Area of Science:
- Mathematical Biology
- Cancer Research
- Genetics
Background:
- Most human cancers arise from accumulated genetic and epigenetic alterations within a single cell.
- Tumorigenesis progresses from initial changes to aggressive and invasive phenotypes.
- Understanding cancer initiation dynamics is crucial for tumor evolution and incidence data.
Purpose of the Study:
- To develop a novel mathematical framework for studying cancer initiation processes.
- To investigate the dynamics of cancer initiation and its dependence on mutational fitness distribution.
- To assess the impact of life expectancy on lifetime cancer incidence.
Main Methods:
- A stochastic process models cell proliferation and (epi)genetic alterations with random fitness changes.
- Cancer initiation is defined as a cell achieving high fitness to escape homeostatic mechanisms.
- A 'race' model considers cancer initiation against patient aging, modeled as a Markov process.
Main Results:
- The framework models cancer initiation dynamics based on mutational fitness distributions.
- It provides a method to evaluate how life expectancy affects lifetime cancer incidence.
- Applied to colorectal cancer, it analyzes initiation probability, timing, and cell profiles based on fitness and lifespan.
Conclusions:
- The model offers insights into cancer initiation influenced by mutation fitness and aging.
- It provides a tool to assess population-level cancer risks considering life expectancy.
- The study highlights the interplay between genetic alterations, cell fitness, and lifespan in tumorigenesis.
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