CHARACTERISTICS OF WOMEN WITH A FAMILY HISTORY OF OVARIAN-CANCER .1. GALACTOSE CONSUMPTION AND METABOLISM

Background. Galactose metabolism may be a risk factor for ovarian canc er based upon evidence that galactose causes ovarian failure and that ovarian cancer arises from premature ovarian failure. This study exami nes galactose-1-phosphate uridyl transferase (GALT) activity in women with a family history of ovarian cancer (FOC) to determine if low GALT activity occurs in women who are at risk for but in whom ovarian canc er has not yet developed. Methods. The authors studied 106 premenopaus al women (FOC patients) with one primary or two second-degree relative s with ovarian cancer compared with 116 age matched control subjects w ithout a family history of ovarian cancer (FOC controls). All women co mpleted questionnaires and had blood drawn to measure GALT activity an d genotype. Results. Mean erythrocyte GALT activity, in micromoles of hexose conversion per hour per gram of hemoglobin was 21.5 in FOC pati ents, significantly lower than the mean of 23.1 observed in FOC contro l subjects, (P = 0.001). FOC patients more frequently displayed the Du arte variant of galactosemia as detected by electrophoresis. In a subs et of 87 patients and 113 control subjects for whom DNA was available, the allelelic frequency of the Duarte variant based upon molecular ge netic detection of the N314D mutation that is associated with the Duar te variant was 15.5% among FOC cases compared with 7.5% among control subjects (P < 0.02). Galactose consumption did not differ between FOC patients and control subjects. Conclusion. Galactose metabolism differ s between women with and without a family history of ovarian cancer, s uggesting that it may be a genetic risk, factor for ovarian cancer, po ssibly mediated through oocyte toxicity from galactose.