Risk assessment for developing gliomas: a comparison of two cytogenetic approaches

Chromosome instability (CIN) measured as chromosome aberrations has long be en suggested as a cancer susceptibility biomarker. Conventional cytogenetic end-points are now being improved by combining molecular methods, which in creases the sensitivity, specificity, and precision of the assay. In this s tudy we examined both spontaneous and gamma -ray induced CIN in lymphocyte cultures from 51 previously untreated glioma patients and 51 age-, sex- and ethnicity-matched controls. CIN was assessed using two parallel methods: ( 1) the mutagen sensitivity (MS) assay and (2) the multicolor fluorescence i n situ hybridization (FISH) assay. The frequency of spontaneous breaks was significantly higher in glioma patients (mean +/- S.D., 2.12 +/- 1.07) than in controls (1.24 +/- 0.86, P < 0.001) when using the FISH assay but not t he MS assay (0.019 +/- 0.02 and 0.019 +/- 0.01. respectively; P = 0.915). S imilarly, the frequency of induced chromatid breaks was significantly highe r using the FISH assay (3.39 +/- 1.72) but not the MS assay (0.42 +/- 0.16) in the patients versus controls (2.08 +/- 1.18 and 0.37 +/- 0.15, respecti vely: P < 0.001 and P = 0.101 respectively). By using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (ORs) of 5.13 (95% CI = 2.23-12.1) for spontaneous and 4.86 (95% CI = 2.08-11.4) for induced CIN using the FISH assay, whereas the ORs were 1.32 (95% CI = 0.49-3.58) and 1.28 (95% CI = 0.59-2.80) for spontaneous and induced CIN us ing the MS assay. There was also a significant increase in the frequency of hyperdiploid cells in the glioma cases which could only be detected using the FISH assay (OR = 4.0, 95% CL = 0.9-17.0). By combining both methods an estimated risk of 7.0 (95% CI = 1.7-25.6) was observed. There was no correl ation between the breaks detected by the two methods suggesting that each m ethod is a measure of a different event. The results indicate that using th e multicolor FISH assay for detection of CIN in peripheral blood lymphocyte s in glioma patients is a more useful marker for risk assessment. (C) 2001 Elsevier Science B.V. All rights reserved.