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Frailty modeling of bimodal age-incidence curves of nasopharyngeal carcinoma in low-risk populations.

Haugen M, Bray F, Grotmol T, Tretli S, Aalen OO, Moger TA - Biostatistics (2009)

Bottom Line: We have developed a multiplicative frailty model that allows for the demonstrated points of inflection at ages 15-24 and 65-74.The bimodal frailty model has 2 independent compound Poisson-distributed frailties and gives a significant improvement in fit over a unimodal frailty model.The results are critically compared and discussed in the context of existing knowledge of the epidemiology and pathogenesis of NPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, PO Box 1122 Blindern, N-0317 Oslo, Norway. marion.haugen@medisin.uio.no

ABSTRACT
The incidence of nasopharyngeal carcinoma (NPC) varies widely according to age at diagnosis, geographic location, and ethnic background. On a global scale, NPC incidence is common among specific populations primarily living in southern and eastern Asia and northern Africa, but in most areas, including almost all western countries, it remains a relatively uncommon malignancy. Specific to these low-risk populations is a general observation of possible bimodality in the observed age-incidence curves. We have developed a multiplicative frailty model that allows for the demonstrated points of inflection at ages 15-24 and 65-74. The bimodal frailty model has 2 independent compound Poisson-distributed frailties and gives a significant improvement in fit over a unimodal frailty model. Applying the model to population-based cancer registry data worldwide, 2 biologically relevant estimates are derived, namely the proportion of susceptible individuals and the number of genetic and epigenetic events required for the tumor to develop. The results are critically compared and discussed in the context of existing knowledge of the epidemiology and pathogenesis of NPC.

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Related in: MedlinePlus

Observed (discrete points) and 25 bootstrap (continuous curves) age-specific incidence rates per 100 000 person–years for both sexes in North America and Japan. Vertical lines are included to emphasize the rates in age groups 15–24 and 65–74.
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fig2: Observed (discrete points) and 25 bootstrap (continuous curves) age-specific incidence rates per 100 000 person–years for both sexes in North America and Japan. Vertical lines are included to emphasize the rates in age groups 15–24 and 65–74.

Mentions: Figure 2 presents 25 bootstrap age-incidence curves, used to calculate bootstrap confidence intervals, together with the observed values. The estimated incidence rates are given by replacing the parameters in (2.4) with their estimated values. These graphs are presented on a semilog-scale to highlight the bimodality. We see less variation for North America than Japan, especially up to the first peak, and the fit is also somewhat better for the former area. This is expected as North America has the highest number of person–years at risk and Japan the lowest (see Table 1). North America contributes therefore the most to the likelihood function and hence the parameter estimates.


Frailty modeling of bimodal age-incidence curves of nasopharyngeal carcinoma in low-risk populations.

Haugen M, Bray F, Grotmol T, Tretli S, Aalen OO, Moger TA - Biostatistics (2009)

Observed (discrete points) and 25 bootstrap (continuous curves) age-specific incidence rates per 100 000 person–years for both sexes in North America and Japan. Vertical lines are included to emphasize the rates in age groups 15–24 and 65–74.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2697345&req=5

fig2: Observed (discrete points) and 25 bootstrap (continuous curves) age-specific incidence rates per 100 000 person–years for both sexes in North America and Japan. Vertical lines are included to emphasize the rates in age groups 15–24 and 65–74.
Mentions: Figure 2 presents 25 bootstrap age-incidence curves, used to calculate bootstrap confidence intervals, together with the observed values. The estimated incidence rates are given by replacing the parameters in (2.4) with their estimated values. These graphs are presented on a semilog-scale to highlight the bimodality. We see less variation for North America than Japan, especially up to the first peak, and the fit is also somewhat better for the former area. This is expected as North America has the highest number of person–years at risk and Japan the lowest (see Table 1). North America contributes therefore the most to the likelihood function and hence the parameter estimates.

Bottom Line: We have developed a multiplicative frailty model that allows for the demonstrated points of inflection at ages 15-24 and 65-74.The bimodal frailty model has 2 independent compound Poisson-distributed frailties and gives a significant improvement in fit over a unimodal frailty model.The results are critically compared and discussed in the context of existing knowledge of the epidemiology and pathogenesis of NPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, PO Box 1122 Blindern, N-0317 Oslo, Norway. marion.haugen@medisin.uio.no

ABSTRACT
The incidence of nasopharyngeal carcinoma (NPC) varies widely according to age at diagnosis, geographic location, and ethnic background. On a global scale, NPC incidence is common among specific populations primarily living in southern and eastern Asia and northern Africa, but in most areas, including almost all western countries, it remains a relatively uncommon malignancy. Specific to these low-risk populations is a general observation of possible bimodality in the observed age-incidence curves. We have developed a multiplicative frailty model that allows for the demonstrated points of inflection at ages 15-24 and 65-74. The bimodal frailty model has 2 independent compound Poisson-distributed frailties and gives a significant improvement in fit over a unimodal frailty model. Applying the model to population-based cancer registry data worldwide, 2 biologically relevant estimates are derived, namely the proportion of susceptible individuals and the number of genetic and epigenetic events required for the tumor to develop. The results are critically compared and discussed in the context of existing knowledge of the epidemiology and pathogenesis of NPC.

Show MeSH
Related in: MedlinePlus