Epidemiological evaluation of cytogenetic biomarkers as potential surrogate end-points for cancer.

Various occupational exposures have been monitored by chromosomal aberrations, sister chromatid exchanges and micronuclei in peripheral blood lymphocytes. During the last decade, epidemiological studies have evaluated whether any of these markers foreshadows cancer risk. Results from Nordic, Italian and Czech cohorts support an approximately twofold cancer risk among subjects with high frequencies of chromosomal aberrations, but no such association was seen for any of the other biomarkers. The estimated attributable proportion of high frequencies of chromosomal aberrations for overall cancer risk is 0.25, which gives a quantitative estimate of the chromosomal aberration assay as a surrogate endpoint of cancer. The results from the different cohort studies are contradictory in terms of whether or not the predictive value of the chromosomal aberration assay for cancer is differential with respect to occupational exposure to clastogens. Genetic susceptibility factors are known to affect the frequency of chromosomal aberrations in peripheral blood lymphocytes. It is quite possible that such factors might also affect the frequency of chromosomal aberrations directly or might modify the impact of exposures to clastogen. There is no other biomarker for general cancer risk that is applicable to healthy subjects from the general population with such a high attributable proportion. However, at present only a simplified and tentative model can be proposed for the role of the chromosomal aberration marker in the pathogenesis of cancer.