Genetic and environmental factors in colorectal carcinogenesis

The molecular genetic mechanisms of colorectal cancer are among the best understood of any common cancer. Recent research has identified mutated tumor suppressor genes and oncogenes as normal tissue progresses from benign to malignant, and the novel mismatch repair genes involved in a specific form of hereditary colorectal cancer as well as a significant percentage of sporadic cases. This information has led to a better understanding of the inheritance of large bowel cancer, as well as a model of tumorigenesis which proposes a multistep process as colonic epithelial cells progress from their normal state through successive stages of adenoma to malignancy. Exogenous factors such as fiber and fat are important modifiers of inherited risk. Dietary factors may influence the carcinogenic process by modifying intestinal transit time, altering the flow and recycling of bile, or changing the intestinal bacterial flora composition. A number of studies have also suggested the modulation of risk in both hereditary syndromes and sporadic cases with certain micronutrients or medications like nonsteroidal anti-inflammatories.