Figure 1.

The proportion of mutation carriers has been measured for women in group A (familial cases) and for women in group B+D (controls). The proportion of mutation carriers is not known for cases without a family history (group C) and, therefore, is not known for women in group A+C. The authors have tried to estimate, in effect, the relative proportion of carriers between groups A+C and B+D, so as to estimate the relative risk associated with having a mutation for the average woman. To do so they have invoked a multiplicative polygenic model. Whatever model is used, however, the absolute risk prediction for women with a strong family history will be about the same. Although the absolute risk prediction for women without a strong family history may well differ depending on the assumptions of the fitted model, in practice this may not matter because only women with a strong family history are likely to be tested for these mutations.