Chromosomal Aberration in Peripheral Blood Lymphocytes of Healthy Subjects and Risk of Cancer

Abstract

The pioneering papers of Theodor Boveri opened the way to extensive research on the mechanism linking chromosomal abnormalities to the pathogenesis of cancer. As a result of this effort, robust theoretical and empirical evidence accumulated, and an increased cancer risk was postulated in healthy subjects with high levels of chromosomal aberrations (CA). The first cohort study which directly evaluated the presence of this association was carried out within the framework of a collaborative study in northern Europe in 1994. Subjects classified as having high frequency of CA showed incidence rates that were more twice those of the general population. The results of this first study were replicated a few years later in a parallel research initiative carried out in Italy, and the subsequent pooled analysis of these two cohorts published in 1998 refined the quantitative estimate of the CA–cancer association. More recent results referring to cohorts in the Czech Republic (2005) and in five European countries (2007) contributed further evidence, suggesting a stronger association with chromosome-type aberrations. A pooled analysis of all cohort studies published involving more that 22,000 subjects from 11 countries has been carried out within the framework of the European project Cytogenetic Biomarkers and Human Cancer Risk, and preliminary results are discussed. The leading priorities to be addressed in the field are the application of existing evidence to the control of occupational and environmental exposure to genotoxic agents, and the evaluation of individual cancer risk assessment procedures based on markers of chromosome damage.