Mutagen sensitivity exhibits a dose-response relationship in case- control studies

We have been quantitating, as a marker of cancer susceptibility, induced chromatid breaks in lymphocyte cultures exposed to chemical mutagens. This report highlights the consistency of the results from two case-control studies, using different methods of presenting the data. In both the lung cancer case-control study, which used bleomycin, a radiomimetic agent, as the test mutagen, and the melanoma study, which used 4-nitroquinoline-oxide, an UV-mimetic agent, the mean number of breaks/cell was significantly higher in the cases compared with the controls. When the data were dichotomized at the 75th percentile of breaks in the control populations, significantly elevated adjusted odds ratios (3.7 and 5.0, respectively) were detected. Dose-response relationships were evident in both studies when the data were categorized by quartiles of breaks/cell in the controls, with highest risk estimates being in the top quartile of induced breaks. The potential for extending this assay to other cancer sites, using a variety of test mutagens, is exciting.