Frailty modeling of the bimodal age-incidence of Hodgkin lymphoma in the Nordic countries.

Background: The bimodality of the age-incidence curve of Hodgkin lymphoma (HL) has been ascribed to the existence of subgroups with distinct etiologies. Frailty models can be usefully applied to age-incidence curves of cancer to aid the understanding of biological phenomena in these instances. The models imply that for a given disease, a minority of individuals are at high risk, compared with the low-risk majority.
Methods: Frailty modeling is applied to interpret HL incidence on the basis of population-based cancer registry data from the five Nordic countries for the period 1993 to 2007. There were a total of 8,045 incident cases and 362,843,875 person-years at risk in the study period.
Results: A bimodal frailty analysis provides a reasonable fit to the age-incidence curves, employing 2 prototype models, which differ by having the sex covariate included in the frailty component (model 1) or in the baseline Weibull hazard (model 2). Model 2 seemed to fit better with our current understanding of HL than model 1 for the male-to-female ratio, number of rate-limiting steps in the carcinogenic process, and proportion of susceptibles; whereas model 1 performed better related to the heterogeneity in HL among elderly males.
Conclusion: The present analysis shows that HL age-incidence data are consistent with a bimodal frailty model, indicating that heterogeneity in cancer susceptibility may give rise to bimodality at the population level, although the individual risk remains simple and monotonically increasing by age.
Impact: Frailty modeling adds to the existing body of knowledge on the heterogeneity in risk of acquiring HL.
(©2011 AACR)