Mutagen sensitivity as a marker of cancer risk

There are measurable differences, genetically determined, in susceptibility to carcinogenic activity. Variation in metabolism of xenobiotic chemicals is one determinant of susceptibility and is attributed to polymorphisms in a number of enzymes. There may also be a wide spectrum of DNA-repair capability within the population. A peripheral lymphocyte assay has been developed in which in vitro bleomycin-induced chromosome breaks provides an indirect measurement of such repair. Mutagen sensitivity as defined by this assay has been shown to be an independent risk factor for tobacco-related malignancies, especially those of the upper aerodigestive tract. Preliminary data also suggest familial aggregation of cancer in mutagen-sensitive patients. Risk assessment is now recognized as a multidisciplinary process, extending beyond the scope of traditional epidemiologic methodology to include biological evaluation of interindividual differences in carcinogenic susceptibility. These susceptibility markers will enable us to identify high-risk population subgroups that can be targeted for intensive primary and secondary preventive strategies.