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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.

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Related in: MedlinePlus

This graph quantitatively shows the agreement between the SEER-9 data and the hypotheses (Equations 3 and 4).The top panel displays the agreement, as measured by a p-value, between lung and colon carcinoma and Equation 3, and between breast carcinoma and Equation 4. In all cases the p-value, representing the probability that one should accept the hypothesis, is greater than 0.001, and in most cases it exceeds 0.01. In contrast, the corresponding graph for prostate carcinoma and Equation 3 shows that the p-value always exceeded 0.01, until 1991 when it plunged below that level. Prostate carcinoma, post 1991, clearly cannot be explained by Equation 3, but it is in agreement with Equation 4. The 1991 change corresponds to the widespread implementation of screening for prostate carcinoma using the PSA test.
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pone-0007053-g002: This graph quantitatively shows the agreement between the SEER-9 data and the hypotheses (Equations 3 and 4).The top panel displays the agreement, as measured by a p-value, between lung and colon carcinoma and Equation 3, and between breast carcinoma and Equation 4. In all cases the p-value, representing the probability that one should accept the hypothesis, is greater than 0.001, and in most cases it exceeds 0.01. In contrast, the corresponding graph for prostate carcinoma and Equation 3 shows that the p-value always exceeded 0.01, until 1991 when it plunged below that level. Prostate carcinoma, post 1991, clearly cannot be explained by Equation 3, but it is in agreement with Equation 4. The 1991 change corresponds to the widespread implementation of screening for prostate carcinoma using the PSA test.

Mentions: The parallel routes hypothesis was consistent with the age-specific incidence date for lung and colon carcinomas for all 32 years. However, the results for prostate and breast carcinoma were more complicated. See Figure 2. Detailed graphs of the data, along with the parallel routes hypothesis, are shown for 2003 in Figure 3. A table presenting the fraction of the population that is susceptible to the disease is shown in Table 1.


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

Brody JP - PLoS ONE (2009)

This graph quantitatively shows the agreement between the SEER-9 data and the hypotheses (Equations 3 and 4).The top panel displays the agreement, as measured by a p-value, between lung and colon carcinoma and Equation 3, and between breast carcinoma and Equation 4. In all cases the p-value, representing the probability that one should accept the hypothesis, is greater than 0.001, and in most cases it exceeds 0.01. In contrast, the corresponding graph for prostate carcinoma and Equation 3 shows that the p-value always exceeded 0.01, until 1991 when it plunged below that level. Prostate carcinoma, post 1991, clearly cannot be explained by Equation 3, but it is in agreement with Equation 4. The 1991 change corresponds to the widespread implementation of screening for prostate carcinoma using the PSA test.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0007053-g002: This graph quantitatively shows the agreement between the SEER-9 data and the hypotheses (Equations 3 and 4).The top panel displays the agreement, as measured by a p-value, between lung and colon carcinoma and Equation 3, and between breast carcinoma and Equation 4. In all cases the p-value, representing the probability that one should accept the hypothesis, is greater than 0.001, and in most cases it exceeds 0.01. In contrast, the corresponding graph for prostate carcinoma and Equation 3 shows that the p-value always exceeded 0.01, until 1991 when it plunged below that level. Prostate carcinoma, post 1991, clearly cannot be explained by Equation 3, but it is in agreement with Equation 4. The 1991 change corresponds to the widespread implementation of screening for prostate carcinoma using the PSA test.
Mentions: The parallel routes hypothesis was consistent with the age-specific incidence date for lung and colon carcinomas for all 32 years. However, the results for prostate and breast carcinoma were more complicated. See Figure 2. Detailed graphs of the data, along with the parallel routes hypothesis, are shown for 2003 in Figure 3. A table presenting the fraction of the population that is susceptible to the disease is shown in Table 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