CHROMOSOMAL-ABERRATIONS IN LYMPHOCYTES PREDICT HUMAN CANCER - A REPORT FROM THE EUROPEAN STUDY-GROUP ON CYTOGENETIC BIOMARKERS AND HEALTH (ESCH)

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 id ea that increased cytogenetic damage reflects an enhanced cancer risk. Nordic and Italian cohorts have been established to evaluate this hyp othesis, and analyses presented previously have shown a positive trend between CA frequency and increased cancer risk. We now report on a po oled analysis of updated data for 3541 subjects examined for CAs, 2703 for SCEs, and 1496 for MN. To standardize for interlaboratory variati on, the results for the various cytogenetic end points were trichotomi zed on the basis of the absolute value distribution within each labora tory as ''low'' (1-33 percentile), ''medium'' (34-66 percentile), or ' 'high'' (67-100 percentile). In the Nordic cohort, there was an elevat ed standardized incidence ratio (SMR) for all cancer among subjects wi th high CA frequency [1.53; 95% confidence interval (CI), 1.13-2.05] b ut not for those with medium or low CA frequency. In the Italian cohor t, 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 hazar ds models gave no evidence that the effect of CAs on total cancer inci dence/mortality was modified by gender, age at test, or time since tes t. No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further suppo rts our previous observation on the cancer predictivity of the CA biom arker, 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 l ymphocytes is a relevant biomarker for cancer risk in humans, reflecti ng either early biological effects of genotoxic carcinogens or individ ual cancer susceptibility.