Mutagen sensitivity: a biological marker of cancer susceptibility.

We intend to continue our exploration of the bleomycin assay as a biological marker for the development of environmentally induced cancers. The impetus for such efforts would be enhanced through effective integration of cancer screening and intervention to achieve diminished cancer mortality. Currently, we are integrating combining bleomycin sensitivity screening to chemopreventive therapy against second primary malignancies in head and neck cancer patients. Previous studies have demonstrated that cis-retinoic acid, the agent used in our chemopreventive trial, is effective in such circumstances (35). Our purpose is to identify a high-risk subpopulation through application of the bleomycin sensitivity assay and then demonstrate that we can modulate the carcinogenic process with cis-retinoic acid. The use of genetic markers clearly enhances the power and precision of epidemiological research. The preventive implications of precise and valid markers for carcinogen sensitivity are obvious. We are aware of the need for extensive validation of the assay and for rigorously designed and conducted epidemiological studies. The strength of the association between cancer risk and mutagen sensitivity, despite the inherent problems in the size and design of the studies, is noteworthy. The thesis that chromosome instability and defective DNA repair may underlie susceptibility to environmental carcinogenesis is plausible and presents a promising avenue for further multidisciplinary research.