Grant: Doctoral Research Award - PA: RPP - Newfoundland and Labrador

Our understanding of cancer susceptibility genes has been greatly enhanced through the study of families that show genetic heritability for specific cancers. Genes for cancer susceptibility play a particularly important role in the etiology of pediatric cancers, as they appear at a time of life when the impact of environmental factors on cancer risk is very low. However, the investigational power to identify genetic determinants for cancer susceptibility may be limited if the cancer is rare in the human population. My research focuses on a particular gene that contributes to spontaneous ovarian granulosa cell (GC) tumour susceptibility in inbred female mice, as a model genetic system for the development of pediatric ovarian tumours that appear with low frequency in infants and young girls. The genetic region under investigation is located on mouse Chromosome 4, and has been shown to be fundamental for ovarian tumour susceptibility. In addition, previous research has shown that this region is responsive to the steroid precursor dehydroepiandrosterone (DHEA), such that treatment with DHEA increases the overall frequency of ovarian tumour appearance. The mouse model indicates a specific gene target for DHEA exists in the mammalian ovary, and in the correct genetic context, this gene supports ovarian tumour initiation in the cells of the ovarian follicle. The identification of the tumour susceptibility gene active in the mouse model will provide specific gene candidates for further investigation in human cases of pediatric GC tumours. Through this research, my ultimate goal is to shed light on the etiological basis of a disease for which such information is severely lacking.