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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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The breast carcinoma disparity between African-American and white women is not due to breast carcinoma A, which occurs at exactly the same rate, but solely due to a difference in breast carcinoma B.The data are from the SEER-17 database during the year 2000 [17]. In each case, the measured incidence is represented by a point and the 95% confidence intervals by error bars. The dark solid lines represents predicted incidence levels based upon the hypothesis, Equation 4, which is the sum of breast carcinoma A and breast carcinoma B indicated by the other curves.
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pone-0007053-g004: The breast carcinoma disparity between African-American and white women is not due to breast carcinoma A, which occurs at exactly the same rate, but solely due to a difference in breast carcinoma B.The data are from the SEER-17 database during the year 2000 [17]. In each case, the measured incidence is represented by a point and the 95% confidence intervals by error bars. The dark solid lines represents predicted incidence levels based upon the hypothesis, Equation 4, which is the sum of breast carcinoma A and breast carcinoma B indicated by the other curves.

Mentions: I found that the age-specific incidence is consistent with the hypothesis that breast carcinoma A has no racial disparity, while breast carcinoma B incidence has substantial racial disparity. See Figure 4. Breast carcinoma B accounts for three quarters of the cases of breast cancer in the United States. A test that could distinguish breast carcinoma B from breast carcinoma A might give promising prognosis information to many patients.


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

Brody JP - PLoS ONE (2009)

The breast carcinoma disparity between African-American and white women is not due to breast carcinoma A, which occurs at exactly the same rate, but solely due to a difference in breast carcinoma B.The data are from the SEER-17 database during the year 2000 [17]. In each case, the measured incidence is represented by a point and the 95% confidence intervals by error bars. The dark solid lines represents predicted incidence levels based upon the hypothesis, Equation 4, which is the sum of breast carcinoma A and breast carcinoma B indicated by the other curves.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0007053-g004: The breast carcinoma disparity between African-American and white women is not due to breast carcinoma A, which occurs at exactly the same rate, but solely due to a difference in breast carcinoma B.The data are from the SEER-17 database during the year 2000 [17]. In each case, the measured incidence is represented by a point and the 95% confidence intervals by error bars. The dark solid lines represents predicted incidence levels based upon the hypothesis, Equation 4, which is the sum of breast carcinoma A and breast carcinoma B indicated by the other curves.
Mentions: I found that the age-specific incidence is consistent with the hypothesis that breast carcinoma A has no racial disparity, while breast carcinoma B incidence has substantial racial disparity. See Figure 4. Breast carcinoma B accounts for three quarters of the cases of breast cancer in the United States. A test that could distinguish breast carcinoma B from breast carcinoma A might give promising prognosis information to many patients.

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