Frailty modelling of colorectal cancer incidence in Norway: indications that individual heterogeneity in risk is related to birth cohort.

Some cancer types level off or decrease in incidence at older age groups, not following the Weibull hazard rate. This stagnation can be explained by the frailty model, which describes the population effect of mixing individuals who are susceptible, with high risk of cancer, with those that are "non-susceptible", with a low risk of cancer even in the oldest age groups. The aim of the study was to apply a frailty model on colorectal cancer incidence data for the Norwegian population aged 40-99 years, diagnosed 1956-2000. The model provided an acceptable fit to the data. The estimated proportion of susceptibles increased from about 5% to about 24% from the first cohort (1851-1855) to the last cohort (1946-1950), in line with the rise in incidence of the disease during this period. According to the frailty modelling, the estimated number of genetic events necessary for a malignant lesion to develop in the colorectum is seven to eight, which accords with the present knowledge regarding colorectal carcinogenesis. The frailty phenomenon may thus be present in this cancer form. The findings indicate that it is possible to model the development of colorectal cancer in the population based on large heterogeneity in risk between individuals, in such a manner that a small group of individuals are susceptible to develop the disease, whereas the remaining majority have a low susceptibility.