Mathematical modeling the gene mechanism of colorectal cancer and the effect of radiation exposure

Abstract

<abstract> <p>Cancer is the result of continuous accumulation of gene mutations in normal cells. The number of mutations is different in different types of cancer and even in different patients with the same type of cancer. Therefore, studying all possible numbers of gene mutations in malignant cells is of great value for the understanding of tumorigenesis and the treatment of cancer. To this end, we applied a stochastic mathematical model considering the clonal expansion of any premalignant cells with different mutations to analyze the number of gene mutations in colorectal cancer. The age-specific colorectal cancer incidence rates from the Surveillance, Epidemiology and End Results (SEER) registry in the United States and the Life Span Study (LSS) in Nagasaki and Hiroshima, Japan are chosen to test the reasonableness of the model. Our fitting results indicate that the transformation from normal cells to malignant cells may undergo two to five driver mutations for colorectal cancer patients without radiation-exposed environment, two to four driver mutations for colorectal cancer patients with low level radiation-exposure, and two to three driver mutations for colorectal cancer patients with high level radiation-exposure. Furthermore, the net growth rate of the mutated cells with radiation-exposure was is higher than that of the mutated cells without radiation-exposure for the models with two to five driver mutations. These results suggest that radiation environment may affect the clonal expansion of cells and significantly affect the development of tumors.</p> </abstract>