Peripheral blood methylation profiling to predict familial ovarian cancer.

OBJECTIVE

Familial cancer appears at a young age and its incidence is increasing. About 12% of familial ovarian cancer cases are associated with mutations (BRCAm). In this study, we investigated methylation may predict ovarian cancer in those with a family history of cancer (FHC) but without mutations (BRCAwt).

METHODS

Using peripheral blood DNA from 55 subjects without a history of cancer [cancer(-)] and 52 ovarian cancer patients, we examined promoter methylation through bisulfite sequencing of the promoter and expressed the results as the cumulative methylation index. Then, we evaluated the promoter methylation according to germline mutations.

RESULTS

methylation was more prevalent in the BRCAm cancer(-) group than in the BRCAwt cancer(-) group and ovarian cancer patients (p=0.031 and p=0.019, respectively). In the BRCAwt cancer(-) group, methylation was more prevalent in those with an FHC than in those without one and in the BRCAm cancer(-) group with an FHC (p=0.001 and p<0.001, respectively).

CONCLUSION

Our data suggest a predictive role of methylation profile for ovarian cancer in those without a history of cancer but with an FHC. methylation has important implications for diagnostic and predictive testing of those with BRCAwt cancer(-) status with FHC.