Heredity, molecular genetics and colorectal cancer: a review

It is estimated that the hereditary polyposis and non-polyposis colorectal cancer (CRC) syndromes, which have an autosomal dominant pattern of inheritance, represent less than 10% of the total CRC burden. Thus, more than 90% of all cases of CRC have previously been considered to arise 'sporadically', with no identifiable genetic link. However, recent clinical evidence now suggests that a significant proportion of CRC seen in the general population may involve an inherited genetic susceptibility. Therefore, constructing an accurate family tree on all patients with a family history of CRC is an essential part of identifying families with an increased risk for CRC who could then be offered screening. Also, molecular genetic study of colorectal adenomas and carcinomas has led to a proposed genetic model of colorectal tumorigenesis which involves interactions between oncogenes and tumour suppressor genes. This information has important potential implications for screening, determining prognosis and for providing multiple targets for altering the sequence of malignant transformation.