In 1992, the investigators began a population-based case-control study of ovarian cancer in eastern Massachusetts and New Hampshire to identify factors affecting risk through a pathway of oocyte-depletion and gonadotropin stimulation. Consumption and metabolism of milk sugar (galactose) was of interest based on evidence that this sugar is toxic to oocytes. Homozygosity for a mutation known as N314D of galactose transferase (GALT) or heterozygosity for mutations that more severely affect activity such as Q188R are found to increase risk for ovarian cancer, especially for endometrioid and clear cell (E/CC) types. Risk factors for these cancers also included earlier onset of, more regular, and shorter cycles--a pattern indicative of greater opportunity for retrograde menstruation and endometriosis, a possible precursor of E/CC cancers. Their search for other genetic factors revealed that 20% of ovarian cancers occurring in Jewish women at any age and 37.5% in Jewish women diagnosed
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