Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

Abstract

Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07-1.60] and in the high (RR = 1.41; 95% CI = 1.16-1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34-3.68). The strongest association was found for stomach cancer [RR(medium) = 1.17 (95% CI = 0.37-3.70), RR(high) = 3.13 (95% CI = 1.17-8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.

Fig. 1.

Country-specific RR of cancer by frequency of CAs. RR was adjusted for gender, age, time since test, job exposure and smoking habit and was expressed in log scale to improve the readability of the figure. Symbols indicate RR by CA category, bars represent CIs. Reference category is the low tertile. RRs from Denmark could not be estimated because no cancer cases occurred in the reference group.

Fig. 2.

Kaplan–Meier curves for total cancer incidence (International Classification of Diseases IX 140–208) tertile of CA frequency based on pooled data from 11 European cohorts. Cancer-free probability refers to time from CA test to the first cancer diagnosis.