gamma-radiation sensitivity and risk of glioma

Background. About 9% of human cancers are brain tumors, of which 90% are gl iomas. gamma -Radiation has been identified as a risk factor for brain tumo rs. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to gamma -radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared th e gamma -radiation sensitivity of lymphocytes from glioma patients with tho se from control subjects and investigated the association between mutagen s ensitivity and the risk for developing glioma. Methods: We used a mutagen s ensitivity assay (an indirect measure of DNA repair activity) to assess chr omosomal damage. We gamma -irradiated (1.5 Gy) short-term lymphocyte cultur es from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured f or 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitos is. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided. Results: We observe d a statistically significantly higher frequency of chromatid breaks per ce ll 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 ce ll in control subjects) as the cut point for defining mutagen sensitivity a nd adjusting for age, sex, and smoking status, we found that mutagen sensit ivity 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 divi ded into tertiles, the relative risk for glioma increased from the lowest t ertile to the highest tertile (trend test, P < .001). Conclusion: gamma -Ra diation-induced mutagen sensitivity of lymphocytes may be associated with a n increased risk for glioma, a result that supports our earlier preliminary findings.