Transmission of X-linked Ovarian Cancer: Characterization and Implications

We recently reported evidence that a strong, BRCA-independent locus on the X-chromosome may contribute to ovarian cancer predisposition in families ascertained from the Familial Ovarian Cancer Registry (Buffalo, NY, USA). While it has been estimated that approximately 20% of all ovarian cancer cases are hereditary, it is possible that a significant proportion of cases previously believed to be sporadic may, in fact, be X-linked. Such X-linked disease has a distinct pattern; it implies that a father will necessarily pass a risk allele to each of his daughters, increasing the prevalence of cancers clustered within a family. X-chromosome inactivation further influences the expression of X-linked alleles and may represent a novel target for screening and therapy. Herein, we review the current literature regarding X-linked ovarian cancer and interpret allele transmission-based models to characterize X-linked ovarian cancer and develop a framework for clinical and epidemiological familial ascertainment to inform the design of future studies.