What Causes It Environmental factors thought to contribute to the development of colorectal cancers include diet (high in saturated fat, low in fiber and possibly low in calcium) and lack of exercise. It is most common in industrialized countries with high standards of living. It is becoming more common in Japan as consumption of fats increases.
One percent of colon cancers are related to an inherited condition called familial polyposis in which multiple polyps begin to appear in childhood and adolescence. Given enough time, most affected individuals will develop cancer.
Several genetic factors linked to colorectal cancer have been found. Ras gene mutations, largely in the k-ras gene resulting from environmental causes rather than being passed on genetically, are found in half of all people with colorectal adenomas and cancers. The tumor-suppressor gene p53 on chromosome 17 seems to be inactivated in most cases. A second tumor-suppressor gene, called DCC, for Deleted in Colon Cancer, has been found on chromosome 18, and other genetic abnormalities have been found on chromosome 5. These may be important for tumor suppression. A defective gene dubbed MSH2 has been located on chromosome 2. Three other genes, mutations of MLH1, PMS1 and PMS2, are also known to influence inherited forms of colon cancer. It has been postulated that these gene defects are responsible for up to two-thirds of the inherited forms of colon cancer. It is possible that when these genetic defects are fully evaluated, family members could be screened and tested for detection of early colon cancer. Once a polyp has one of these chromosome changes, other "hits" to the cell may cause cancers to develop.
