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      A Generalized Beta Model for the Age Distribution of Cancers: Application to Pancreatic and Kidney Cancer

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          Abstract

          The relationships between cancer incidence rates and the age of patients at cancer diagnosis are a quantitative basis for modeling age distributions of cancer. The obtained model parameters are needed to build rigorous statistical and biological models of cancer development. In this work, a new mathematical model, called the Generalized Beta (GB) model is proposed. Confidence intervals for parameters of this model are derived from a regression analysis. The GB model was used to approximate the incidence rates of the first primary, microscopically confirmed cases of pancreatic cancer (PC) and kidney cancer (KC) that served as a test bed for the proposed approach. The use of the GB model allowed us to determine analytical functions that provide an excellent fit for the observed incidence rates for PC and KC in white males and females. We make the case that the cancer incidence rates can be characterized by a unique set of model parameters (such as an overall cancer rate, and the degree of increase and decrease of cancer incidence rates). Our results suggest that the proposed approach significantly expands possibilities and improves the performance of existing mathematical models and will be very useful for modeling carcinogenic processes characteristic of cancers. To better understand the biological plausibility behind the aforementioned model parameters, detailed molecular, cellular, and tissue-specific mechanisms underlying the development of each type of cancer require further investigation. The model parameters that can be assessed by the proposed approach will complement and challenge future biomedical and epidemiological studies.

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          A New Theory on the Cancer-inducing Mechanism

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            Models for temporal variation in cancer rates. I: Age-period and age-cohort models.

            A main concern of descriptive epidemiologists is the presentation and interpretation of temporal variations in cancer rates. In its simplest form, this problem is that of the analysis of a set of rates arranged in a two-way table by age group and calendar period. We review the modern approach to the analysis of such data which justifies traditional methods of age standardization in terms of the multiplicative risk model. We discuss the use of this model when the temporal variations are due to purely secular (period) influences and when they are attributable to generational (cohort) influences. Finally we demonstrate the serious difficulties which attend the interpretation of regular trends. The methods described are illustrated by examples for incidence rates of bladder cancer in Birmingham, U.K., mortality from bladder cancer in Italy, and mortality from lung cancer in Belgium.
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              Understanding the effects of age, period, and cohort on incidence and mortality rates.

              T Holford (1991)
              Time trends for population-based disease rates often are summarized by using direct adjustment by period of diagnosis or death. Similarly, the effect of age often is presented graphically as age-specific rates for a given period of diagnosis. These approaches may be necessary if there is an absence of long-term data, as they provide a natural way for annually updating information when monitoring trends, or they may be a convenient way of summarizing a large amount of data (7, 10, 11, 39, 45). However, these summaries only can adjust for the effect of age in a given period; they implicitly ignore the cohort effect. The effect of cohort is an important factor in understanding time trends for many diseases. Thus, it is not advisable to use data analytic strategies that routinely ignore it. Another alternative to modeling is to give a graphical presentation of the age-specific rates themselves. As I noted in the introduction, some of the first analyses to identify the effect of cohort on diseases, such as tuberculosis and lung cancer, relied entirely on a graphical analysis. Although graphs certainly are an important part of the interpretation of time trends, it would be a mistake to limit your analysis to impressions of points on a graph. For example, such a perusal would not give an objective indication of the statistical significance of a particular pattern. Regression analysis forces us to recognize a fundamental problem with interpreting time trends in disease rates--a problem that you should remember, even when trying to understand a graphical display of time trends in age-specific rates.
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                Author and article information

                Journal
                Cancer Inform
                101258149
                Cancer Informatics
                Libertas Academica
                1176-9351
                2009
                4 August 2009
                : 7
                : 183-197
                Affiliations
                Eppley Cancer Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska, 68198-6805. Email: ssherm@ 123456unmc.edu
                Article
                cin-2009-183
                2730181
                19718452
                03e6de62-5ea8-42e0-867b-98af262404d9
                © 2009 The authors.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

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                Categories
                Original Research

                Oncology & Radiotherapy
                histopathology,aging,incidence rates,cancer
                Oncology & Radiotherapy
                histopathology, aging, incidence rates, cancer

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