Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively in the last decades to survey human exposure to genotoxic agents. The conceptual basis for this approach has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. The predictive value of these tests for subsequent cancer risk has been recently evaluated by two cohort studies of cancer mortality and incidence carried out in Italy and in five North European countries. In this paper we report the update of both cohorts. In the new follow-up, a total of 64 cancer deaths out of 2019 subjects in the Italian cohort and 127 new cases of cancer out of 3182 subjects in the Nordic cohort were observed. The cytogenetic endpoints studied were CA (chromosomal aberrations), SCE (sister chromatid exchanges) and MN (micronuclei). In order to take into account the interlaboratory variation of absolute values, the results were trichotomized within each laboratory into three strata: low (1-33 percentile), medium (34-66 percentile), or high (67-100 percentile). The association between chromosomal damage and cancer risk was evaluated through SMR (standardized mortality ratio) for Italy and SIR (standardized incidence ratio) for the Nordic countries. National mortality/incidence cancer rates (age, sex and calendar-year specific) were used as reference. A linear trend of SMRs and SIRs according to CA level was found in both cohorts for the "All Cancers" cause (p < 0.01). In the Italian cohort it was also possible to analyze some specific cancer sites: a significant increase of SMR among subjects with a high level of CA with respect to the general population was found for lung cancers and lymphatic and hematopoietic tissue cancers. Contrariwise, no association between cancer mortality/incidence and SCE or MN frequency was observed. Findings from this study support the existence of an association between CA frequency and cancer risk.
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