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Cancer Risk in Humans Predicted by Increased Levels of Chromosomal Aberrations in Lymphocytes: Nordic Study Group on the Health Risk of Chromosome Damage¹

Department of Occupational and Environmental Medicine [L. H., S. S.] and Department of Clinical Genetics [F. M.], Lund University, S-221 85 Lund, Sweden; Norwegian Radium Hospital, N-0310 Oslo, Norway [A. B.]; Department of Occupational Medicine, Telemark Central Hospital, N-3710, Skien, Norway [I-L. H.]; Department of Medical Genetics, Odense University, DK-5000 Odense, Denmark [S. H.]; Department of Occupational Medicine, Central Hospital, S-30185 Halmstad, Sweden [B. H.]; National Institute of Occupational Health, DK-2100 Copenhagen, Denmark [L. K.]; Department of Environmental Medicine, Centre for Nutrition and Toxicology, Karolinska Institute, S-14157 Huddinge, Sweden [B. L.]; Institute of Occupational Health, SF-00290 Helsinki, Finland [K. L., M. S.]; Institute of Medical Genetics, University of Umeå, S-90185 Umeå, Sweden [I. N.]; National Institute of Occupational Health, S-17184 Solna, Sweden [C. R.]; and Finnish Center for Radiation and Nuclear Safety, SF-00101 Helsinki, Finland [S. S.]

Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange or micronuclei in PBL. In order to standardize for the interlaboratory variation, the results were trichotomized for each laboratory into three strata: low (1–33 percentile), medium (34–66 percentile), or high (67–100 percentile). In this second follow-up, a total of 85 cancers were diagnosed during the observation period (1970–1991). There was no significant trend in the standardized incidence ratio with the frequencies of sister chromatid exchange or micronuclei, but the data for these parameters are still too limited to allow firm conclusions. There was a statistically significant linear trend (P = 0.0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant blomarker of future cancer risk.

¹ Supported by the Nordic Council of Ministers, the Swedish Work Environment Fund, the Swedish Cancer Society, and the Medical Faculty, Lund University.

² To whom requests for reprints should be addressed, at Department of Occupational and Environmental Medicine, University Hospital, S-221 85 Lund, Sweden.

³ Project coordinators.

Received 12/28/93. Accepted 4/ 5/94.

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