Mathematical Models of Age and Ultraviolet Effects on the Incidence of Skin Cancer Among Whites in the United States

Fears, Thomas R.; Scotto, Joseph; Schneiderman, Marvin A.

doi:10.1093/oxfordjournals.aje.a112400

Cited by 212 publications

(91 citation statements)

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“…4A). This time-dose effect is consistent with the observation that cancer incidence rates depend more strongly on age than on cumulative radiation dosage (28). Stochastic cell behavior has important implications for the acquisition of the additional oncogenic mutations.…”

Section: Discussionsupporting

confidence: 87%

“…Once formed the pool of preneoplastic cells is self-maintaining, until further UVB exposure occurs, when exponential growth resumes. Such behavior may be a key contributor to the observed supralinear increase in the incidence of nonmelanoma skin cancer with age in humans (28). These results suggest that individuals with the highest lifetime dose of UVB have the most to gain from avoiding further sun exposure: a summer of sun or a week in a suntan parlor has a far greater effect on skin that already contains a significant population of p53 mutant cells.…”

Section: Discussionmentioning

confidence: 89%

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Stochastic fate ofp53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia

Klein

Brash

Jones

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

106

108

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UV B (UVB) radiation induces clones of cells mutant for the p53 tumor suppressor gene in human and murine epidermis. Here we reanalyze large datasets that report the fate of clones in mice subjected to a course of UVB radiation, to uncover how p53 mutation affects epidermal progenitor cell behavior. We show that p53 mutation leads to exponential growth of clones in UV-irradiated epidermis; this finding is also consistent with the size distribution of p53 mutant clones in human epidermis. Analysis of the tail of the size distribution further reveals that the fate of individual mutant cells is stochastic. Finally, the data suggest that ending UVB exposure results in the p53 mutant cells adopting the balanced fate of wild-type cells: the loss of mutant cells is balanced by proliferation so that the population of preneoplastic cells remains constant. We conclude that preneoplastic clones do not derive from long-lived, self-renewing mutant stem cells but rather from mutant progenitors with random cell fate. It follows that ongoing, low-intensity UVB radiation will increase the number of precancerous cells dramatically compared with sporadic, higherintensity exposure at the same cumulative dose, which may explain why nonmelanoma skin cancer incidence depends more strongly on age than on radiation dosage. Our approach may be applied to determine cell growth rates in clonally labeled material from a wide range of tissues including human samples.cancer | stem cells | stochastic fate

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 89%

Stochastic fate ofp53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia

Klein

Brash

Jones

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

106

108

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“…Simple observation (even in humans) suggests that this number increases with age and environmental stress factors (e.g., solar irradiation can be invoked as causative agents [7,8,14,23]). Variability in the underlying genetic mechanisms responsible for the spots is likely, at least in different races, as well as in susceptibility to environmental stress factors.…”

Section: Discussionmentioning

confidence: 99%

A comparison between Poisson and zero-inflated Poisson regression models with an application to number of black spots in Corriedale sheep

Naya

Urioste²,

Chang

et al. 2008

Genet. Sel. Evol.

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-Dark spots in the fleece area are often associated with dark fibres in wool, which limits its competitiveness with other textile fibres. Field data from a sheep experiment in Uruguay revealed an excess number of zeros for dark spots. We compared the performance of four Poisson and zero-inflated Poisson (ZIP) models under four simulation scenarios. All models performed reasonably well under the same scenario for which the data were simulated. The deviance information criterion favoured a Poisson model with residual, while the ZIP model with a residual gave estimates closer to their true values under all simulation scenarios. Both Poisson and ZIP models with an error term at the regression level performed better than their counterparts without such an error. Field data from Corriedale sheep were analysed with Poisson and ZIP models with residuals. Parameter estimates were similar for both models. Although the posterior distribution of the sire variance was skewed due to a small number of rams in the dataset, the median of this variance suggested a scope for genetic selection. The main environmental factor was the age of the sheep at shearing. In summary, age related processes seem to drive the number of dark spots in this breed of sheep.zero-inflated Poisson / sheep / spot / posterior predictive ability / Bayesian hierarchical model

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“…These findings imply that most of the TP53 mutant cells in human epidermis arise by UV-driven proliferation of pre-existing mutant cells rather than new mutations. The mutant cell population will self-maintain over the winter, when there is little UV exposure, and expand during the summer, perhaps explaining the supralinear relationship between non-melanoma skin cancer incidence and life time UV dose, as cancer risk is dependent on the proportion of TP53 mutant cells [43,44]. Use of sunblock should thus be lifelong, as the proportionate reduction in risk will increase with age [41].…”

Section: However In Mouse Intestine Krasmentioning

confidence: 99%

Mutation, clonal fitness and field change in epithelial carcinogenesis

2014

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Developments in lineage tracing in mouse models have revealed how stem cells maintain normal squamous and glandular epithelia. Here we review recent quantitative studies tracing the fate of individual mutant stem cells which have uncovered how common oncogenic mutations alter cell behaviour, creating clones with a growth advantage that may persist long term. In the intestine this occurs by a mutant clone colonizing an entire crypt, whilst in the squamous oesophagus blocking differentiation creates clones that expand to colonize large areas of epithelium, a phenomenon known as field change. We consider the implications of these findings for early cancer evolution and the cancer stem cell hypothesis, and the prospects of targeted cancer prevention by purging mutant clones from normal-appearing epithelia.

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Mathematical Models of Age and Ultraviolet Effects on the Incidence of Skin Cancer Among Whites in the United States

Cited by 212 publications

References 0 publications

Stochastic fate ofp53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia

Stochastic fate ofp53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia

A comparison between Poisson and zero-inflated Poisson regression models with an application to number of black spots in Corriedale sheep

Mutation, clonal fitness and field change in epithelial carcinogenesis

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