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Gestational mutations and carcinogenesis.

Authors
Meza-R; Luebeck-EG; Moolgavkar-SH
Source
Math Biosci 2005 Oct; 197(2):188-210
NIOSHTIC No.
20028874
Abstract
We present a mathematical formulation to evaluate the effects of gestational mutations on cancer risk. The hazard or incidence function of cancer is expressed in terms of the Probability Generating Function (PGF) of the number of normal and mutated cells at birth. Using Filtered Poisson Process Theory, we obtain the PGF for several models for the accumulation of gestational mutations. In particular, we develop expressions for the hazard function when one or two successive mutations could occur during gestation. We also calculate the hazard when the background gestational mutation rates are increased due to exposure to mutagens, such as prenatal radiation. To illustrate the use of our models, we apply them to colorectal cancer in the SEER database. We find that the proportion of cancer risk attributable to developmental mutations depends on age and that it could be quite significant when gestational mutation rates are high. The analysis of the SEER data also shows that gestational mutations could contribute to inter-individual variations in colorectal cancer risk.
Keywords
Carcinogens; Carcinogenicity; Carcinogenesis; Cancer; Risk-factors; Risk-analysis; Models; Mutagens; Exposure-levels; Exposure-assessment
Contact
Department of Applied Mathematics, University of Washington, and Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P.O. Box 19024, Seattle, WA 98109-1024, USA
CODEN
MABIAR
Publication Date
20051001
Document Type
Journal Article
Funding Type
Grant
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007864
Issue of Publication
2
ISSN
0025-5564
Source Name
Mathematical Biosciences
State
WA
Performing Organization
Fred Hutchinson Cancer Research Center
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