Mutation Research 514 (2002) 165–176 Increased risk of cancer in radon-exposed miners with elevated frequency of chromosomal aberrations Zdenek Smerhovsky a,∗ , Karel Landa a , Pavel R " Ossner a , Dagmar Juzova a , Marek Brabec a , Zdena Zudova b , Nora Hola c , Hana Zarska d , Emilie Nevsimalova e a National Institute of Public Health, Srobarova Str. 48, 10042 Prague 10, Czech Republic b Regional Institute of Hygiene, Brno, Pellicova 29, 60200 Brno, Czech Republic c Regional Institute of Hygiene, Moskevska 15, 40048 Usti nad Labem, Czech Republic d Regional Center of the State Office for Nuclear Safety, Habrovice 52, 40340 Usti nad Labem, Czech Republic e Ward of Occupational Diseases of Masaryk Hospital, Na kabate 285, 40113 Usti nad Labem, Czech Republic Received 21 August 2001; received in revised form 30 October 2001; accepted 6 November 2001 Abstract In spite of the extensive use of cytogenetic analysis of human peripheral blood lymphocytes in the biomonitoring of exposure to various mutagens and carcinogens, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 1323 cytogenetic assays and 225 subjects examined because of occupational exposures to radon (range of exposure from 1.7 to 662.3 working level month (WLM)). Seventy-five subjects were non-smokers. We found 36 cases of cancer in this cohort. Chromatid breaks were the most frequently observed type of aberrations (mean frequency 1.2 per 100 cells), which statistically significantly correlated with radon exposure (Spearman’s correlation coefficient R = 0.22, P< 0.001). Also, the frequency of aberrant cells (median of 2.5%) correlated with radon exposure (Spearman’s correlation coefficient R = 0.16, P< 0.02). Smoking and silicosis were not associated with results of cytogenetic analyses. The Cox regression models, which accounted for the age at time of first cytogenetic assay, radon exposure, and smoking showed strong and statistically significant associations between cancer incidence and frequency of chromatid breaks and frequency of aberrant cells, respectively. A 1% increase in the frequency of aberrant cells was paralleled by a 62% increase in risk of cancer (P< 0.000). An increase in frequency of chromatid breaks by 1 per 100 cells was followed by a 99% increase in risk of cancer (P< 0.000). We obtained similar results when we analyzed the incidence of lung cancer and the incidence other than lung cancer separately. Contrary to frequency of chromatid breaks and frequency of aberrant cells, the frequency of chromatid exchanges, and chromosome-type aberrations were not predictive of cancer. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Chromosomal aberrations; Radon; Cancer risk; Epidemiology ∗ Corresponding author. Tel.: +42-2-6708-2759; fax: +42-2-6731-1236. E-mail address: zdsm@szu.cz (Z. Smerhovsky). 1. Introduction The occurrence of structural chromosomal aberra- tions in surrogate tissues such as human peripheral 1383-5718/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S1383-5718(01)00328-X