Evaluating the number of stages in development of squamous cell and adenocarcinomas across cancer sites using human population-based cancer modeling.
Abstract
BACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical
and molecular characteristics. We evaluated the characteristics of carcinogenesis
by modeling the age patterns of incidence rates of ACs and SCCs of various organs
to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL
FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry
(1973-2003) were analyzed by fitting several biologically motivated models to observed
age patterns. A frailty model with the Weibull baseline was applied to each age pattern
to provide the best fit for the majority of cancers. For each cancer, model parameters
describing the underlying mechanisms of carcinogenesis including the number of stages
occurring during an individual's life and leading to cancer (m-stages) were estimated.
For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis
model to test the stability of the estimates. For the majority of studied cancers,
the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers
of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number
of m-stages were more strongly associated with the AC/SCC subtype than with the organ:
9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared
to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05
between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten
m-stages. The sensitivity analyses of the model parameters demonstrated the stability
of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters
capable of representing the number of stages of cancer development occurring during
individual's life was applied to the large population data on incidence of ACs and
SCCs. The model revealed that the number of m-stages differed by cancer subtype being
more strongly associated with ACs/SCCs histotype than with organ/site.
Type
Journal articleSubject
AdenocarcinomaAdult
Age Distribution
Aged
Aged, 80 and over
Carcinoma, Squamous Cell
Cohort Studies
Esophageal Neoplasms
Female
Humans
Incidence
Lung Neoplasms
Middle Aged
Models, Statistical
SEER Program
Sensitivity and Specificity
United States
Uterine Cervical Neoplasms
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https://hdl.handle.net/10161/14850Published Version (Please cite this version)
10.1371/journal.pone.0037430Publication Info
Kravchenko, Julia; Akushevich, Igor; Abernethy, Amy P; & Lyerly, H Kim (2012). Evaluating the number of stages in development of squamous cell and adenocarcinomas
across cancer sites using human population-based cancer modeling. PLoS One, 7(5). pp. e37430. 10.1371/journal.pone.0037430. Retrieved from https://hdl.handle.net/10161/14850.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Amy Pickar Abernethy
Adjunct Professor in the Department of Medicine
Amy P. Abernethy, MD PhDDirector, Center for Learning Health Care Director, Duke Cancer
Care Research Program Professor of Medicine, Department of Medicine, Division of Medical
Oncology, Duke University School of Medicine Associate Professor of Nursing, Duke
University School of NursingDr. Abernethy, a hematologist/oncologist and palliative
care physician, is Professor of Medicine in the Duke University School of Medicine,
Director of the Duke Center for Learn
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Igor Akushevich
Research Professor in the Social Science Research Institute
Herbert Kim Lyerly
George Barth Geller Distinguished Professor of Immunology
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