Trans-organ and Intra-organ Cancer Susceptibility
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Risk of sporadic cancer varies greatly in the population and is influenced by many cancer susceptibility genes collectively. In spite of the large number of cancer susceptibility loci detected in humans or in animal models for each type of cancer, most of the underlying causal genes and the molecular pathways involved have not been clarified. Therefore many aspects of the functions of cancer susceptibility genes in an organ (intra-organ susceptibility) remain unknown; and the functions of cancer susceptibility genes across organs (trans-organ susceptibility) have never been studied systematically. We performed three studies to answer these questions from different perspectives, utilizing the recombinant congenic (RC) strains, a tool specially designed for dissecting multi-gene diseases. In the first study, we present five sets of data on genetic architecture of colon and lung cancer susceptibility in mice, humans and rats. They collectively show that the majority of genes for colon and lung cancer susceptibility are linked pair-wise and are likely identical or related. In the second study, we identified three novel loci controlling mammary tumor susceptibility in mice, using crosses between RC strains carrying the ErbB2/HER2/neu transgene. And in the third study, we improved the mapping of lung cancer susceptibility locus Sluc20, using strains constructed from the RC strains that carried additional recombinants in the Sluc20 region. We also identified a strong genetic control on tumor regionality by Sluc20. Our data provided valuable information to predict the cancer susceptibility studies in humans, which may potentially improve the prevention, detection and treatment of cancer.
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