Role of modifying alleles in the heritable colorectal cancer syndromes with polyps.

It is proposed, based on in vitro studies on hereditary colorectal cancer syndromes (adenomatosis of the colon and rectum, ACR), that the presence/absence of specific abnormal culture phenotypes within and between such ACR kindreds will demonstrate the interaction of a modifying allele with its proposed major polyposis gene, influencing expression of this major gene, at least in vitro. Such in vitro evidence would suggest that the variability of clinical phenotype was due, at least in part, to such gene-gene interaction and this should be considered as well as the influence of enviornmental agents on the development of both pre-malignant lesions and clinical cancer in such cancer-prone families.