[Etiopathogenic factors in colorectal cancer. Genetic and clinical features (first of 2 parts)].
BACKGROUND
Colorectal Cancer (CRC) is the second cause of death in Spain, reaching the first place in non-smoking population. It is also the tumour with the greatest one-year incidence. The last few years some reduction in its incidence along with a greater 5-year average survival has been observed.


METHODS
Most CRCs develop from benign polyps. Vogelstein's hypothesis suggests an orderly progression from normal mucosa, to a small polyp, to a large polyp and finally to a CRC. In this progression transforming cells will be increasingly charged with molecular alterations.
20% of CRCs have a genetic background although only a fourth of these are genetically based. The APC (or FAP) gene mutation is one of the earlier events that can be seen in tumour progression. When this mutation appears in the germ line it renders Familial Adenomatose Polyposis Syndrome (that evolves to CRC in a 100% of cases) or to the Gardner Syndrome (if it has extracolonic expressions). The p53 mutation is a late event in cellular transformation but it makes a rapid accumulation of mutations an easier process and it confers advantages for survival of the tumour cells. Mutations in the genes implicated in microsatellite instability are related to DNA error repair; their clinical correlates are the Lynch I and II syndromes. Other important genes related to CRC are DCC and ras. CLINICAL FACTORS: Inflammatory Bowel Disease (particularly Crohn's disease) is the most important clinical factor, it may enhance basal risk 30 times. Other risk factors are: previous malignant conditions, pelvic irradiation and previous surgery (cholecystectomy and ureterosigmoidostomy). The endocrinologic factors have a rising importance and so hormonal substitution therapy for menopause and multiparity can provide some protection. The use of NSAIDs can also be protective (specially COX-2 inhibitors).


CONCLUSIONS
It is important that people who are identified as having a high risk for developing a CRC are subjected to a strict clinical and endoscopic follow-up in order to be able to identify an incipient tumour or to practice prophylactic surgery. The use of hormonal substitution therapy or anti COX-2 NSAIDs can be future useful chemoprophylactic agents.
Casimiro
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Abbott Laboratories, Departamento Médico, Josefa Valcárcel, 48, 28027 Madrid. cesar.casimiro@abbott.com
D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics; D006801:Humans
Factores etiopatogénicos en el cáncer colorrectal. Aspectos genéticos y clínicos (primera de dos partes).