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Lausanne: EPFL, 2006

Carcinogenesis is commonly described as a multistage process. In a first step, a stem cell is transformed via a series of mutations into an intermediate cell having a growth advantage. Under favorable conditions, such a cell will give rise to a clone of initiated cells. Eventually, further alterations may transform a cell out of this clone into a malignant tumor cell. A mechanistic model of this process is given by the widely used two-stage clonal expansion model (TSCE). In this thesis, we take up a generalization of the TSCE, and study, how to introduce the concept of population heterogeneity into the model. We use mixture modeling, which allows to describe frailty in a biologically meaningful way. In a first part, we focus on theoretical properties of the extended model. Especially identifiability is discussed extensively. In a second part, we fit the model to human cancer incidence data. We analyze a situation, in which maximum likelihood estimation fails, and describe alternatives for statistical inference. The applications show that good fits are achieved only when the mixing distribution separates the population clearly into a large, virtually immune group, and into a small, high risk group.

Keywords: Multistage carcinogenesis ; Heterogeneity ; Frailty modeling ; Mixture modeling ; Carcinogénèse ; Modèle à étapes multiples ; Hétérogénéité ; Modèles de fragilité ; Modèles mélangés Thèse École polytechnique fédérale de Lausanne EPFL, n° 3611 (2006)Section de mathématiquesFaculté des sciences de baseInstitut de mathématiquesChaire de statistique appliquéeJury: Annette Kopp-Schneider, Anthony C. Davison, Luigi Preziosi Public defense: 2006-9-8 Reference doi:10.5075/epfl-thesis-3611Print copy in library catalog

Autor: Gsteiger, SandroAdvisor: Morgenthaler, Stephan

Fuente: https://infoscience.epfl.ch/record/86088?ln=en

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