Multiple markers have been implicated in the pathogenesis of human malignancies. Point mutations in the ras oncogene have been identified in colorectal and lung carcinomas and have recently been identified in shed epithelial cells found in stool specimens from patients with colorectal carcinoma. Alterations in carbohydrate antigen expression have also been found in malignancies and may be useful markers of neoplastic change. To determine the potential usefulness of the detection of oncogene mutations or activation, or changes in carbohydrate antigen expression using markers detected on epithelial cells shed in stool, archived stool specimens from patients with documented colorectal cancer will be analyzed using polymerase chain reaction (PCR), and these findings will be correlated with the markers present in the archived surgical material. This archive was collected during a case-control study of colorectal cancer conducted at the National Naval Medical Center, Bethesda, Maryland; Walter Reed Army Hospital; and George Washington University Hospital, Washington, D.C. from 1985-87. The information obtained will be coupled with the previously collected epidemiologic data and Tumor Registry data for survival information to determine the potential usefulness for screening or prognostic purposes. Published reports have suggested that genomic p53 mutations may be present in individuals with an inherited susceptibility to several type of cancer, including but not limited to Li-Fraumeni syndrome. A similar study using genomic DNA from whole blood collected during a case-control study of lung cancer is anticipated evaluating markers of susceptibility to lung cancer, which may be used to define appropriate populations for rational screening. The success of early detection of cancer is dependent upon the ability to intervene successfully at that early stage to prevent the morbidity and mortality associated with cancer and standard therapy. In collaboration with Dean Cole at Los Alamos National Laboratory we propose to evaluate a new photoactive porphyrin compound for local ablation of abnormal bronchial epithelium.
