Molecular genetics of familial colorectal cancer

IN WESTERN COUNTRIES, colorectal cancer is consistently among the leading malignancies in both incidence and mortality. Although diet is the major risk factor in most cases of colorectal cancer, an underlying predisposition, at least toward adenomas, may contribute significantly. In retrospective studies, patients with colorectal cancer are more likely to have a close relative similarly afflicted. In other reports, an increased probability of having an affected relative occurred if the index case was young. Beyond reliance on these empiric risk estimates is the opportunity to identify families in which an inherited predisposition to colorectal adenomas and/or cancer occurs. These conditions, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer and their variants, will be discussed, with emphasis placed on the dramatic recent advances in molecular genetics of these disorders and their implications for improved management.