Molecular pathways in colorectal cancer

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and accounts for the second highest number of cancer related deaths in Australia, the third worldwide and of increasing importance in Asia. It arises through cumulative effects of inherited genetic predispositions and environmental factors. Genomic instability is an integral part in the transformation of normal colonic or rectal mucosa into carcinoma. Three molecular pathways have been identified: these are the chromosomal instability (CIN), the microsatellite instability (MSI), and the CpG Island Methylator Phenotype (CIMP) pathways. These pathways are not mutually exclusive, with some tumors exhibiting features of multiple pathways. Germline mutations are responsible for hereditary CRC syndromes (accounting for less than 5% of all CRC) while a stepwise accumulation of genetic and epigenetic alterations results in sporadic CRC. This review aims to discuss the genetic basis of hereditary CRC and the different pathways involved in the process of colorectal carcinogenesis.