The aim of a primary screening system is to detect premalignant lesions and carcinomas when amenable to "curative" surgery. Although a number of "classical" tumor markers have acquired potential for clinical management, none is presently adequate for presymptomatic diagnosis or screening. In colorectal carcinoma, the screening potential of carcinoembryonic antigen (CEA), the gastrointestinal-related antigen, CA19-9, and other more recently characterized "biochemical markers" is virtually nonexistent, even in patients at high risk to develop the disease. Promising new leads are beginning to emerge from somatic cell genetic and molecular biological approaches. In common with other epithelial neoplasms, perturbations in oncogene expression have been demonstrated in colorectal cancers, and probably reflect important events in malignant transformation and progression. Studies of oncogene expression have, however, not yet yielded clinically useful information. Recently, an intensive search for specific chromosomal and gene abnormalities in the hereditary colon cancer syndromes led to the location of the familial adenomatous polyposis (FAP) gene at chromosome 5q21-q22. Significant is that the loss of alleles on chromosome 5 has also been observed in the tumor cells of at least 20% of sporadic colon cancer patients. This type of association between constitutional genetic change and genetic aberration in the cells of sporadic tumors is reminiscent of other malignant diseases with a genetic component (e.g., retinoblastoma and Wilms' tumor).(ABSTRACT TRUNCATED AT 250 WORDS)