New stochastic carcinogenesis model with covariates: an approach involving intracellular barrier mechanisms.

Akushevich, Igor

Veremeyeva, Galina

Kravchenko, Julia

Ukraintseva, Svetlana

Arbeev, Konstantin

Akleyev, Alexander V

Yashin, Anatoly I

United States

2017-06-06T15:39:21Z

2017-06-06T15:39:21Z

2012-03

In this paper we present a new multiple-pathway stochastic model of carcinogenesis with potential of predicting individual incidence risks on the basis of biomedical measurements. The model incorporates the concept of intracellular barrier mechanisms in which cell malignization occurs due to an inefficient operation of barrier cell mechanisms, such as antioxidant defense, repair systems, and apoptosis. Mathematical formalism combines methodological innovations of mechanistic carcinogenesis models and stochastic process models widely used in studying biodemography of aging and longevity. An advantage of the modeling approach is in the natural combining of two types of measures expressed in terms of model parameters: age-specific hazard rate and means of barrier states. Results of simulation studies allow us to conclude that the model parameters can be estimated in joint analyses of epidemiological data and newly collected data on individual biomolecular measurements of barrier states. Respective experimental designs for such measurements are suggested and discussed. An analytical solution is obtained for the simplest design when only age-specific incidence rates are observed. Detailed comparison with TSCE model reveals advantages of the approach such as the possibility to describe decline in risk at advanced ages, possibilities to describe heterogeneous system of intermediate cells, and perspectives for individual prognoses of cancer risks. Application of the results to fit the SEER data on cancer risks demonstrates a strong predictive power of the model. Further generalizations of the model, opportunities to measure barrier systems, biomedical and mathematical aspects of the new model are discussed.

https://www.ncbi.nlm.nih.gov/pubmed/22200574

S0025-5564(11)00187-8

1879-3134

https://hdl.handle.net/10161/14847

eng

Elsevier BV

Math Biosci

10.1016/j.mbs.2011.12.002

Cell Transformation, Neoplastic

Computer Simulation

Humans

Models, Biological

Models, Statistical

SEER Program

Stochastic Processes

New stochastic carcinogenesis model with covariates: an approach involving intracellular barrier mechanisms.

Journal article

Arbeev, Konstantin|0000-0002-4195-7832

https://www.ncbi.nlm.nih.gov/pubmed/22200574

16

30

1

Center for Population Health & Aging

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Population Research Center

Duke Population Research Institute

Institutes and Centers

Institutes and Provost's Academic Units

Physics

Sanford School of Public Policy

School of Medicine

Social Science Research Institute

Staff

Surgery

Surgery, Surgical Sciences

Trinity College of Arts & Sciences

University Institutes and Centers

Published

236