5571 Background: Ovarian cancer patients with germline BRCA1 or BRCA2 (gBRCA1/2) mutations frequently respond to multiple lines of chemotherapy. Having noticed significant myelosuppression during chemotherapy in gBRCA1/2 patients we wished to determine whether this was a chance finding or related to a heterozygous gene dosage effect in the bone marrow. Methods: gBRCA1/2 ovarian cancer patients from Edinburgh, Glasgow and Dundee were identified and matched for chemotherapy regimen, dose and age to controls from the Edinburgh Ovarian Cancer Database. Case notes and transfusion service records were analysed for chemotherapy details, haematology results, G-CSF use, red cell and platelet transfusions during first line chemotherapy. Results: Of 91 gBRCA1/2 patients, 35 patients were excluded who had previously received cytotoxic chemotherapy (mostly for breast cancer) or unusual chemotherapy regimens unable to be matched to controls. 56 were matched to controls. Baseline haematological indices were similar. There was a significant difference in the fall in haemoglobin levels from baseline to cycle 4 in gBRCA1/2 patients compared to controls (12.23% v 5.14%, p = 0.0005) and gBRCA1/2 patients had longer delays during their chemotherapy (mean 7.73 v 4.51 days, p = 0.0375) and more dose reductions for haemotoxicity (14 v 4 p = 0.0011). gBRCA1/2 were more likely to have a red cell transfusion (19 v 11, p = 0.099), and received more red cells (69 v 31 units, p = 0.0318). G-CSF was required in 3 BRCA patients versus 0 controls. Differences in platelet and white cell counts at cycle 4 were not significant. Conclusions: Patients with ovarian cancer and germline BRCA1/2 mutations were more likely to have significant falls in haemoglobin levels and require red cell transfusions and to experience delays during chemotherapy. This susceptibility to anaemia may be a hemizygous BRCA1/2 gene dosage effect manifest in the bone marrow and may have implications for the optimisation of cytotoxic and PARP inhibitor therapy in this patient group.
THE GENETIC BASIS OF DOSAGE COMPENSATION OF ALCOHOL DEHYDROGENASE-1 IN MAIZE
