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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

Estimated proportion of susceptible males and females per 100 000 person–years (circles) in (a) peak 1 and (b) peak 2. The error bars give the log-transformed 95% confidence intervals.
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fig4: Estimated proportion of susceptible males and females per 100 000 person–years (circles) in (a) peak 1 and (b) peak 2. The error bars give the log-transformed 95% confidence intervals.

Mentions: In Figure 4, we have plotted the estimated proportion of susceptible males and females per 100000 person–years, with error bars giving the 95% confidence intervals. These intervals are log transformed since the proportions of susceptible individuals are relatively small and the coefficients of variation for these values are relatively large. In all 5 aggregated low-risk areas, for both peaks, there is a higher frailty proportion among males than females, reflecting the higher incidence among males. In peak 1, North America has the lowest proportion of frail individuals and India the highest. The hazard ratio at age 19.5 gave significantly higher risk for India than North America. North and west Europe has the lowest proportion of frail individuals and Australia the highest in the second peak.


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)

Estimated proportion of susceptible males and females per 100 000 person–years (circles) in (a) peak 1 and (b) peak 2. The error bars give the log-transformed 95% confidence intervals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Estimated proportion of susceptible males and females per 100 000 person–years (circles) in (a) peak 1 and (b) peak 2. The error bars give the log-transformed 95% confidence intervals.
Mentions: In Figure 4, we have plotted the estimated proportion of susceptible males and females per 100000 person–years, with error bars giving the 95% confidence intervals. These intervals are log transformed since the proportions of susceptible individuals are relatively small and the coefficients of variation for these values are relatively large. In all 5 aggregated low-risk areas, for both peaks, there is a higher frailty proportion among males than females, reflecting the higher incidence among males. In peak 1, North America has the lowest proportion of frail individuals and India the highest. The hazard ratio at age 19.5 gave significantly higher risk for India than North America. North and west Europe has the lowest proportion of frail individuals and Australia the highest in the second peak.

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