Estimation of familial recurrence risk of malignancy: Application of liability threshold model in genetic counseling.

Abstract

Apart from some Mendelian-inherited tumors, malignancies are multifactorial diseases, and reported data are often the only sources to estimate familial recurrence risk. Edwards' approximation formula has provided one way forward, but it uses estimates only from incidence in the general population, and is thus too simple to be widely utilized for complex individual instances. On the other hand, the heritability of malignancies has been estimated from twin studies, and it has been found that different tumors have rather different heritability. In the present study, I report a method to estimate the familial recurrence risk from the population incidence and the heritability of each malignancy, applying Falconer's liability threshold model. Trial calculations with this method using literature data support its potential use. For example, the calculation indicated that the relative risk of developing stomach cancer is 2.1 times in the first-degree relatives than in the general population whereas for leukemia the risks were estimated to be 7.4 times and 2.9 times for the first- and the second-degree relatives, respectively. Thus, the proposed method could be a useful tool in genetic counseling for risk of malignancies.