This study is designed to contribute to the understanding of genetic and molecular mechanisms associated with large bowel polyposis and cancer in family groups. Phenotypic expressions of preneoplasia will be detected in cells from populations having intestinal polyposis coli, the Gardner syndrome and solitary discrete polyps. Data will be used to develop differential criteria and to predict which children carry the gene defect at an age before clinical signs appear. Specific objectives and methods are: 1. To keep the family-medical histories of kindreds involved in this study up-to-date, and to maintain cooperative arrangements for continuing the study of inheritance as well as clinical and subclinical phenotypes. 2. To develop methods for clinical diagnosis of intestinal polyposis and the Gardner syndrome by: (a) examination of family members for colonic and extracolonic manifestations, particularly early lesions of the mandible, (b) microautoradiography of cells from various levels of the digestive tract, (c) observation of atypical and malignant cells from washings of colonic mucosa, (d) culture of cutaneous fibroblasts at different levels of fetal calf serum, (e) transformation of cultured fibroblasts in the presence of oncogenic virus, (f) implantation of cells in athymic mice and observations of resulting lesions, (g) growth characteristics of cells in methocel suspension, (h) responsiveness of lymphocytes in mixed cultures of leukocytes, (i) chromosome heteroploidy or tetraploidy, and (j) quantitation of carcinoembryonic antigen (CEA) in serum, colonic washings and rectal biopsies. 3. To delineate the Gardner syndrome by descriptive characterization and by discovery of basic mechanisms for origin and development of the entity. 4. To determine the kinetics of normal and abnormal cell development in colonic and extra-colonic lesions of Gardner syndrome patients. 5. To extend the investigation to include more families with intestinal polyposis coli, the Gardner syndrome and solitary polyps, as well as other states of polyposis.
NIH ExPorter
NIH ExPorter