Genetic Modifiers of Intitiation and Progression of Mamm

Cancer Epidemiology And Genetics

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Abstract

Recent progress in our laborabory has been significant. During the past year we published the results of our first study of the effect of constitutional polymorphism influencing metastasis. We demonstrated that a single amino acid polymorphism in the gene Sipa1 could modulate the metastatic capacity of mouse mammary tumors by as much as ten-fold. Furthermore we demonstrated, using pilot human epidemiology studies, that polymorphisms in the human ortholog of this gene, SIPA1, were associated with lymphnode status in human breast cancer. These findings were the first published example that genetic inheritance rather that mutation within tumors, plays a major role in progression of human cancer. These results also open up the possibility that it is possible to predicted those patients at risk of metastatic disease prospectively, from normal tissues such as blood. This hypothesis was confirmed by our finding that it was possible, using gene expression profiling, to predicted which animals in our mouse model system were going to develop lung metastasis, based on protein expression profiles.