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Chromosomal Aberrations in Lymphocytes Predict Human Cancer: A Report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH)¹

Department of Occupational and Environmental Medicine, Lund University, S-221 85 Lund, Sweden [L. H., U. S.]; Department of Environmental Epidemiology, Istituto Nazionale per la Ricerca sul Cancro, I-1016132 Genova, Italy [S. B.]; Norwegian Radium Hospital, N-0310 Oslo, Norway [A. B.]; Danish National Institute of Occupational Health, DK-2100 Copenhagen, Denmark [L. E. K.]; Finnish Institute of Occupational Health, FIN-00250 Helsinki, Finland [H. N.]; and National Institute of Work Life, SE-17184 Solna, Sweden [C. R.]

Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN) in peripheral blood lymphocytes have for decades been used as cytogenetic biomarkers to survey genotoxic risks in the work environment. The conceptual basis for this application has been the idea that increased cytogenetic damage reflects an enhanced cancer risk. Nordic and Italian cohorts have been established to evaluate this hypothesis, and analyses presented previously have shown a positive trend between CA frequency and increased cancer risk. We now report on a pooled analysis of updated data for 3541 subjects examined for CAs, 2703 for SCEs, and 1496 for MN. To standardize for interlaboratory variation, the results for the various cytogenetic end points were trichotomized on the basis of the absolute value distribution within each laboratory as "low" (1–33 percentile), "medium" (34–66 percentile), or "high" (67–100 percentile). In the Nordic cohort, there was an elevated standardized incidence ratio (SMR) for all cancer among subjects with high CA frequency [1.53; 95% confidence interval (CI), 1.13–2.05] but not for those with medium or low CA frequency. In the Italian cohort, a SMR in cancer of 2.01 (95% CI, 1.35–2.89) was obtained for those with a high CA frequency level, whereas the SMRs for those with medium or low did not noticeably differ from unity. Cox's proportional hazards models gave no evidence that the effect of CAs on total cancer incidence/mortality was modified by gender, age at test, or time since test. No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk patterns were similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility.

¹ Supported by the European Union Biomed 2 program, the Swedish Medical Research Council, the Swedish Cancer Society, the Swedish Council for Work Life Research, the Academy of Finland, Associazione Italiana per la Ricerca sul Cancro, the Italian Ministry of Health, and the Italian Ministry of the University and of the Scientific and Technological Research.

² To whom requests for reprints should be addressed.

³ Other members of the ESCH include: Alessandra Forni, Istituto di Medicina del Lavoro, Clinica del Lavoro "L. Devoto," Milan University, Milan, Italy; Inger-Lise Hansteen, Department of Occupational Medicine, Telemark Central Hospital, Skien, Norway; Benkt Högstedt, Department of Occupational Medicine, Central Hospital, Halmstad, Sweden; Alicia Huici Montagud, Centro Nacional de Condiciones de Trabajo, Instituto Nacional de Seguridad e Higiene en el Trabajo, Barcelona, Spain; Bo Lambert, Department of Environmental Medicine, Centre for Nutrition and Toxicology, Karolinska Institute, Stockholm, Sweden; Felix Mitelman, Department of Clinical Genetics, Lund University, Lund, Sweden; Ingrid Nordenson, National Institute of Work Life, Umeå, Sweden; Sisko Salomaa, Finnish Center for Radiation and Nuclear Safety, Helsinki, Finland; Staffan Skerfving, Department of Occupational and Environmental Medicine, Lund University, Lund, Sweden.

Received 12/23/97. Accepted 7/17/98.

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