γ-Radiation sensitivity and risk of glioma

Background: About 9% of human cancers are brain tumors, of which 90% are gliomas. γ-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to γ-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the γ-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma. Methods: We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We γ-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided. Results: We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P<.001). Using 0.40 (the median number of chromatid breaks per cell in control subjects) as the cut point for defining mutagen sensitivity and adjusting for age, sex, and smoking status, we found that mutagen sensitivity was statistically significantly associated with an increased risk for glioma (odds ratio = 2.09; 95% CI = 1.43 to 3.06). When the data were divided into tertiles, the relative risk for glioma increased from the lowest tertile to the highest tertile (trend test, P<.001). Conclusion: γ-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.