Evidence that Natural Immunity to Breast Cancer and Prostate Cancer Exists in the Majority of Their Risk Populations Is Predicted by a Novel, Inherently Saturated, Ordered Mutation Model

Abstract

The series of ordered mutations that cause a specific cell to become cancerous is modeled so that the fraction of a risk population (e.g. White men) that has developed a specific cancer (e.g. melanoma) at any age can be calculated. The saturated model constructed and solved here is isomorphic to the physical model describing an ordered chain of radioactive nuclei decays with the exception that it allows for the possibility that a fraction of a risk population may be immune to developing a specific cancer.The simplest model developed here depends on only three independent parameters: the number of ordered mutations necessary for a cell to become cancerous, the fraction of the risk population that is immune to developing a specific cancer and the average time between mutations (a time defined as the mutation lifetime). The values of these independent parameters are determined by fitting the model's cancer incidence function to the cancer incidence data.This model was applied to five widely different cancers: melanoma, pancreatic cancer, female breast cancer, non-Hodgkin lymphoma and prostate cancer. The modeling predicts that all White males in the USA are vulnerable to developing melanoma, five-ordered mutations are required to develop it and the mutation lifetime is 48.3 years. By contrast, the modeling predicts that 80.7% of White females in the USA are immune to developing melanoma, three-ordered mutations are required to develop it and the mutation lifetime is 78.9 years. Remarkably, it was also found that about 70% of females are immune to developing breast cancer and about 70% of males are immune to developing prostate cancer, predictions that fit in with the experimental evidence of cancer immunosurveillance and immunoediting.Clearly, different risk populations can develop the same cancer through different pathways. Delineating the mechanism underlying the prevalence of immunity to specific cancers in specific risk populations should become a research priority. Finding ways of blocking or repairing cellular mutations and/or destroying mutated, potentially cancerous cells would prevent cancers from developing altogether and eliminate a major cause of mortality.1. The saturated, ordered, mutation model of cancer developmentResearch data suggests that a cancerous cell results from an ordered series of random mutations. A potentially cancerous cell spontaneously mutates from one mutation state to another in a definite order until the final mutation causes the cell to become cancerous. Thus, for example, a normal, unmutated cell can only mutate into the first mutation state and no other and cells that are in the first mutation state can only mutate into the second mutation state and no other, etc. It is assumed that the characteristics of the cell in each mutation state are unique and different from the characteristics of the cell in every other mutation state. It is also assumed that a specific cancer results from an ordered series of mutations of a single cell of a specific organ.Clearly, the number of mutatio...

Widespread Immunity to Breast and Prostate Cancers is Predicted by a Novel Model that also Determines Sporadic and Hereditary Susceptible Population Sizes

“…The high prevalence of natural immunity to breast and prostate cancers predicted here and in [1] fits-in with the current concepts of cancer immunosurveillance, part of the more general theory of immunoediting [36,37,38,39,40,41,42].…”

“…Before or after this mutation, a damaging mutation must take place in the gene that stops cell division so that when a cell becomes cancerous it will remain so. Thus, it would appear that a minimum of three (m = 3) ordered mutations are required to cause a normal cell to become cancerous, the same number found to cause melanoma in the White Male risk group [1]. The modeling results here for breast and prostate cancers certainly meet this requirement.…”

“…More recently, a cohort of HIV-infected men between 60 and 70 years old was found to have a 21-fold increased risk for developing prostate cancer [14], suggesting that the immunity to prostate cancer in the majority of men predicted here and in reference [1] could be the result of effective immune system reaction against mutated prostate cells in these men.…”

“…The model used here is a more sophisticated version of the one developed for describing cancers in reference [1] and is completely described in the appendix here for the convenience of the readers. This mutation model constructed here was also used to describe the transition from HIV infection to AIDS [2] and the development of Alzheimers disease [3].…”

“…There are three different types of genes within a cell that are important in determining whether a cell becomes cancerous or not: (1) genes that signal a cell to multiply, (2) genes that stop a cell from multiplying (e.g., the p53 tumor suppressor gene), and (3) genes that repair other damaged (mutated) genes.…”