[Etiology of colorectal cancer].
Colorectal cancer affect the 15% of general population in developed countries. Cancer is a multistep process in which multiple genetic alterations must usually occur in several years. The premalignant step consists of one or multiple aberrant crypts due to hyperproliferation of cells and its shift from the deep third of the crypt to its surface. It has been suggested that abnormality in the APC gene is responsible for this. Furthermore, there exists DNA hypometilation, activation of the gene K-ras and ornithine decarboxylase activity. There is also a loss of MCC gene, that seems to interact with the APC gene. Entire alterations described make possible the Class I adenoma formation. This adenoma, needs the loss of the DCC gene (late stage in the carcinogenesis process), to become a Class II adenoma. The following alteration is deleted and mutation of the p53 gene. There is also an activation of the c-myc oncogene. These two genes are important mechanisms for the conversion of a benign adenoma to a malignant one, adenoma with in situ carcinoma or Class III adenoma. This type of adenoma becomes carcinoma and metastatic stage, throughout inactivation of several tumor suppressor genes. Besides the hereditary APC alteration and other acquired genetic changes as described above there are other associated genetics, antigenics, and enzymes that have an important role in the adenoma-carcinoma sequence. Several carcinogenic factors have been described which also contribute in the adenoma and carcinoma formation: ulcerative colitis, acromegaly, familial history of colonic neoplasia, certain professions, smoking and drinking, consumption of red or processed meat, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
Matos Villalobos
M
M
Unidad de Gastroentérología de la Clínica El Avila, Caracas.
D000236:Adenoma / Q000209:etiology / Q000517:prevention & control; D002278:Carcinoma in Situ / Q000209:etiology / Q000517:prevention & control; D015984:Causality; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000517:prevention & control; D004032:Diet / Q000009:adverse effects; D006801:Humans; D011230:Precancerous Conditions; D012307:Risk Factors