The contribution of inherited predisposition to cancer incidence.

Only a small proportion of cancers, arising in inherited syndromes such as polyposis coli, have an unequivocally inherited basis. Nevertheless, most common cancers show familial clustering, much of which may be due to inherited predisposition. If so, there may be wide variation in genetic susceptibility to common cancers. The precise models of susceptibility are unclear, but for ovarian cancer and breast cancer there is some evidence that a small proportion of cases result from highly penetrant dominant genes. This has been confirmed recently for breast cancer by genetic linkage studies. Clear evidence for genetic susceptibility has been obtained for Hodgkin's disease and nasopharyngeal carcinoma, where the existence of susceptibility genes at the HLA locus has been demonstrated by linkage analysis. These genes could account for the majority of cases of these cancers. Identification of other cancer susceptibility genes should be possible, either directly using linkage analysis, or through identification of constitutional phenotypes related to cancer risk.