Molecular bases of colorectal cancer

Abstract

Worldwide, colorectal cancer (CRC) is a public health problem; it is the third most prevalent cancer in men and the second in women. There are some geographical variations in its incidence, with high rates in many developed countries of Europe, North America and Oceania, and low rates in countries of less developed regions such as Africa and South America. Recent studies on cancer, published by the International Agency for Research on Cancer (IARC), show a rapid increase in the incidence of CRC in developing countries between 1983-1987 and 1998-2002 (1), while in the developed world incidence has stabilized and in many cases decreased (2). Carcinogenesis of CRC is a multiple step process, characterized by high genomic instability that may lead to the accumulation of mutations in proto-oncogenes, tumor suppressor genes, repair machinery failures, epigenetic changes in DNA and production of non-functional proteins; these changes lead to cell proliferation advantages and an increase in cell survival. Genomic instability of CRC occurs through different pathways, the most important of which are: chromosomal instability (CIN), microsatellite instability (MSI) and methylation.