Colorectal cancer is a highly prevalent malignancy worldwide, with an increased incidence in patients diagnosed with inflammatory bowel disorders (IBD). Risk of IBD is strongly influenced by genetic factors, including the IBD5 locus (5q31), harboring the IRF1 gene. Our studies have shown that in the azoxymethane (AOM)/dextran sodium sulfate (DSS) murine model of colitis-associated colorectal cancer (CA-CRC), loss of interferon regulatory factor 1 (Irf1) results in enhanced tumorigenesis. Transcriptome profiling of AOM/DSS treated colons conducted early in the pathogenesis of CA-CRC showed heightened colonic inflammation and leukocyte infiltration in Irf1-/- mice compared to WT controls, well before the appearance of tumors.