Colon cancer is the third leading cause of cancer related death among men and women annually. The American Cancer Society estimated about 141,210 new cases of colon cancer and 49,380 deaths expected in 2011. Prevention of colon cancer is very important and can save millions of dollars spent on treatment. This project is going to help understand whether or not the combination of multiple deficiencies in important genes in tumor suppression pathways will act similar to complete deficiency in these pathways, which eventually lead to developing cancer. Understanding that effect might partially explain the majority of cancer cases that comes from the general population who are not completely deficient in these pathways but yet develop cancer. Thus, results obtained from my studies will broaden our understanding of an individual’s susceptibility to developing cancer. We hypothesize that partial deficiencies in multiple pathways will interact to reduce protection and increase the risk of genotoxic effects of exposure. We predict individuals with similar deficiencies would be at increase risk of cancer. This can be done by creating isogenic cell lines with reduced gene expression for several different genes, creating multiple partial deficiencies. These cells can then be used to measure the effect of exposure to PAH’s. Different combinations of specific gene deficiencies will be created and tested for the magnitude of the effect of PAH exposure.