Colon cancer is the third most common form of cancer and the second leading cause of cancer deaths in the United States. The majority of colorectal cancer (CRC) cases are thought to be sporadic occurrences; often displaying a hereditary influence although a genetic mutation has yet to be identified. Additionally, specific behaviors and environmental factors encountered by an individual increase the risk to sporadic CRC development. Mouse strains exposed to azoxymethane (AOM), an organospecific carcinogen, have differing sensitivities to colon tumor formation. Intercrossed mice of opposing susceptibility phenotypes, provide a model to mimic sporadic colorectal cancer occurrence in the human population. Inbred A/J mice are sensitive to AOM and develop colon tumors, while mice from a genetically diverse strain, Spretus, are resistant to tumor formation. The F1 (AJ /SpretEi) of these two strains that display polar affects to AOM are also resistant to tumors. Interestingly, 40% of mice in the backcrossed N2 generation develop AOM induced tumors. We propose these specific aims to identify susceptibility genes that predispose and individual to cancer formation: 1) Genetically map loci for AOM induced CRC susceptibility. We are genotyping =300 N2 AOM treated mice. It is our intent to genomic regions associated with tumor penetrance, size, and multiplicity. 2) Characterize genetic networks associated with cancer susceptibility to identify candidate modifiers through the analysis of gene expression profiles. RNA extracted from the colons of =138 mice will be used to capture microarray gene expression profiles. Transcript data will be used to identify candidate genes or modifiers of cis and trans acting expression QTLs (eQTLs) involved in colon cancer progression. ? ? ?
| Eversley, Chevonne D; Yuying, Xie; Pearsall, R Scott et al. (2012) Mapping six new susceptibility to colon cancer (Scc) loci using a mouse interspecific backcross. G3 (Bethesda) 2:1577-84 |
| Eversley, Chevonne D; Clark, Tavia; Xie, Yuying et al. (2010) Genetic mapping and developmental timing of transmission ratio distortion in a mouse interspecific backcross. BMC Genet 11:98 |
