Limits...
Parallel routes of human carcinoma development: implications of the age-specific incidence data.

Brody JP - PLoS ONE (2009)

Bottom Line: The age-specific incidence data from most human carcinomas, including those of the colon, lung, prostate, and breast were consistent with the parallel route hypothesis.Furthermore, breast carcinoma has two distinct forms of the disease, and one of these occurs at significantly different rates in different racial groups.I conclude that the parallel route hypothesis is consistent with the age-specific incidence data only if carcinoma occurs in a distinct sub population, while the multi-stage hypothesis is inconsistent with this data.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering University of California Irvine, Irvine, California, United States of America. jpbrody@uci.edu

ABSTRACT

Background: The multi-stage hypothesis suggests that cancers develop through a single defined series of genetic alterations. This hypothesis was first suggested over 50 years ago based upon age-specific incidence data. However, recent molecular studies of tumors indicate that multiple routes exist to the formation of cancer, not a single route. This parallel route hypothesis has not been tested with age-specific incidence data.

Methodology/principal findings: To test the parallel route hypothesis, I formulated it in terms of a mathematical equation and then tested whether this equation was consistent with age-specific incidence data compiled by the Surveillance Epidemiology and End Results (SEER) cancer registries since 1973. I used the chi-squared goodness of fit test to measure consistency. The age-specific incidence data from most human carcinomas, including those of the colon, lung, prostate, and breast were consistent with the parallel route hypothesis. However, this hypothesis is only consistent if an immune sub-population exists, one that will never develop carcinoma. Furthermore, breast carcinoma has two distinct forms of the disease, and one of these occurs at significantly different rates in different racial groups.

Conclusions/significance: I conclude that the parallel route hypothesis is consistent with the age-specific incidence data only if carcinoma occurs in a distinct sub population, while the multi-stage hypothesis is inconsistent with this data.

Show MeSH

Related in: MedlinePlus

This graph compares two different hypotheses for the development of carcinoma with the age-specific incidence data.The multi-stage hypothesis, as represented by the Armitage-Doll model, Equation 2 [51], and parallel route hypothesis, represented by Equation 3. The Armitage-Doll model is an approximation of the differential form of the Poisson process, Equation 1. Using this equation gives , a substantially better, but still clearly unacceptable fit. Thus, the parallel route hypothesis is clearly acceptable, while the multi-stage hypothesis is not. The error bars represent 95% confidence intervals in the measured values.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2743810&req=5

pone-0007053-g001: This graph compares two different hypotheses for the development of carcinoma with the age-specific incidence data.The multi-stage hypothesis, as represented by the Armitage-Doll model, Equation 2 [51], and parallel route hypothesis, represented by Equation 3. The Armitage-Doll model is an approximation of the differential form of the Poisson process, Equation 1. Using this equation gives , a substantially better, but still clearly unacceptable fit. Thus, the parallel route hypothesis is clearly acceptable, while the multi-stage hypothesis is not. The error bars represent 95% confidence intervals in the measured values.

Mentions: The parallel route hypothesis is consistent with the colon carcinoma age-specific incidence data, while the multi-stage hypothesis is not. To determine this, I compared the mathematical representation of the parallel route hypothesis, Equation 3, with the age-specific incidence data. In the same manner, I also compared the mathematical representation of the multi-stage hypothesis (the Armitage-Doll model Equation 2 [4]) with the age-specific incidence data. See Figure 1. (Figure S1 demonstrates that the computer simulations accurately represent the Armitage Doll model.) The specific results are that the probability one should accept the parallel route hypothesis is (, with 52 degrees of freedom), while the probability that one should accept the multi-stage hypothesis, Equation 2, is (, with 53 degrees of freedom), see Figure 1.


Parallel routes of human carcinoma development: implications of the age-specific incidence data.

Brody JP - PLoS ONE (2009)

This graph compares two different hypotheses for the development of carcinoma with the age-specific incidence data.The multi-stage hypothesis, as represented by the Armitage-Doll model, Equation 2 [51], and parallel route hypothesis, represented by Equation 3. The Armitage-Doll model is an approximation of the differential form of the Poisson process, Equation 1. Using this equation gives , a substantially better, but still clearly unacceptable fit. Thus, the parallel route hypothesis is clearly acceptable, while the multi-stage hypothesis is not. The error bars represent 95% confidence intervals in the measured values.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2743810&req=5

pone-0007053-g001: This graph compares two different hypotheses for the development of carcinoma with the age-specific incidence data.The multi-stage hypothesis, as represented by the Armitage-Doll model, Equation 2 [51], and parallel route hypothesis, represented by Equation 3. The Armitage-Doll model is an approximation of the differential form of the Poisson process, Equation 1. Using this equation gives , a substantially better, but still clearly unacceptable fit. Thus, the parallel route hypothesis is clearly acceptable, while the multi-stage hypothesis is not. The error bars represent 95% confidence intervals in the measured values.
Mentions: The parallel route hypothesis is consistent with the colon carcinoma age-specific incidence data, while the multi-stage hypothesis is not. To determine this, I compared the mathematical representation of the parallel route hypothesis, Equation 3, with the age-specific incidence data. In the same manner, I also compared the mathematical representation of the multi-stage hypothesis (the Armitage-Doll model Equation 2 [4]) with the age-specific incidence data. See Figure 1. (Figure S1 demonstrates that the computer simulations accurately represent the Armitage Doll model.) The specific results are that the probability one should accept the parallel route hypothesis is (, with 52 degrees of freedom), while the probability that one should accept the multi-stage hypothesis, Equation 2, is (, with 53 degrees of freedom), see Figure 1.

Bottom Line: The age-specific incidence data from most human carcinomas, including those of the colon, lung, prostate, and breast were consistent with the parallel route hypothesis.Furthermore, breast carcinoma has two distinct forms of the disease, and one of these occurs at significantly different rates in different racial groups.I conclude that the parallel route hypothesis is consistent with the age-specific incidence data only if carcinoma occurs in a distinct sub population, while the multi-stage hypothesis is inconsistent with this data.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering University of California Irvine, Irvine, California, United States of America. jpbrody@uci.edu

ABSTRACT

Background: The multi-stage hypothesis suggests that cancers develop through a single defined series of genetic alterations. This hypothesis was first suggested over 50 years ago based upon age-specific incidence data. However, recent molecular studies of tumors indicate that multiple routes exist to the formation of cancer, not a single route. This parallel route hypothesis has not been tested with age-specific incidence data.

Methodology/principal findings: To test the parallel route hypothesis, I formulated it in terms of a mathematical equation and then tested whether this equation was consistent with age-specific incidence data compiled by the Surveillance Epidemiology and End Results (SEER) cancer registries since 1973. I used the chi-squared goodness of fit test to measure consistency. The age-specific incidence data from most human carcinomas, including those of the colon, lung, prostate, and breast were consistent with the parallel route hypothesis. However, this hypothesis is only consistent if an immune sub-population exists, one that will never develop carcinoma. Furthermore, breast carcinoma has two distinct forms of the disease, and one of these occurs at significantly different rates in different racial groups.

Conclusions/significance: I conclude that the parallel route hypothesis is consistent with the age-specific incidence data only if carcinoma occurs in a distinct sub population, while the multi-stage hypothesis is inconsistent with this data.

Show MeSH
Related in: MedlinePlus