Colon cancer is the second most lethal
cancer; approximately 600,000 people die of it annually in the world. Colon
carcinogenesis generally follows a slow and stepwise process of accumulation of mutations under the influence of environmental and epigenetic factors. To adopt a personalized (tailored)
cancer therapy approach and to improve current strategies for prevention, diagnosis, prognosis, and
therapy overall, advanced understanding of molecular events associated with colon
carcinogenesis is necessary. A contemporary approach that combines genetics, epigenomics, and signaling pathways has revealed many genetic/genomic alterations associated with
colon cancer progression and their relationships to a
genomic instability phenotype prevalent in
colon cancer. In this review, we describe the relationship between gene mutations associated with colon
carcinogenesis and a
genomic instability phenotype, and we discuss possible clinical applications of
genomic instability studies. Colon
carcinogenesis is associated with frequent mutations in several pathways that include
phosphatidylinositol 3-kinase,
adenomatous polyposis coli, p53 (TP53), F-box and WD repeat domain containing 7,
transforming growth factor-β, chromosome cohesion, and K-RAS. These genes frequently mutated in pathways affecting
colon cancer were designated
colon cancer (CAN) genes. Aberrations in major colon CAN genes have a causal relationship to
genomic instability. Conversely,
genomic instability itself plays a role in colon
carcinogenesis in experimental settings, as demonstrated in transgenic mouse models with high
genomic instability. Thus, there is a feedback-type relationship between CAN gene mutations and
genomic instability. These genetic/genomic studies have led to emerging efforts to apply the knowledge to
colon cancer prognosis and to targeted
therapy.