Genetics of colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most important neoplasms not only for its prevalence but also for its incidence, accounting for 10% of all the neoplasms in the USA. However, its mortality remained unaffected in the last 50 years. Since Morson described the adenoma-carcinoma sequence for the first time in 1978, the elucidation of the molecular mechanisms involved in the pathogenesis of CRC became intensively studied and many progresses were obtained. Several genes, like APC, DCC and p53, among others, were identified as participants of the adenoma-carcinoma sequence. They are involved in the multi-step process of the tumorigenesis, where the accumulation of genetic mutations in unstable cells represents the most important factor, which ends up rising the cancer. There are two basic types of CRC : the sporadic, that accounts for 85% of the total of cases of CRC ; and the familal, with about 15 % of the cases, which includes the Adenomatous Polyposi of the Colum (APC) and the Hereditary Non-Polyposis Colorectal Câncer (HNPCC). The mechanisms of action of such genes are now being described and research is being made to determine their prognostic value. One expect that the complete elucidation of such mechanisms will allow a decrease not only on the mortality, but also on the social impact imposed by such disease. Moreover, altemative treatments for surgery seems possible by gene therapy. Therefore, it is imperative for gastrointestinal surgeons and physicians to be familiarized with the genetics of the colorectal cancer.