Chapter 9: Biomarkers of Individual Susceptibility: Genetic Polymorphisms and their Interplay with Micronucleus Frequencies

Micronuclei (MN) have been widely used to assess genotype–phenotype associations. The advantages of the MN assay as a valuable tool for this approach lie in its wide application for measuring DNA damage in human populations, the wide range of events detected by this assay, its extensive validation and reliability for human biomonitoring, its cancer risk predictivity, and the recent implementation of automated methods for MN detection. MN can be induced as a result of chromosome breakage due to unrepaired or misrepaired DNA lesions, or chromosome malsegregation due to mitotic malfunction, and they may arise after exposure to clastogens or aneugens. The link between genotypes, which take into account inter-individual differences in response to genotoxic exposure, and the occurrence of MN, which quantifies the extent of genetic damage caused by environmental/occupational exposures, has been extensively reported in the literature. In this chapter we aimed to briefly review and discuss the association between frequencies of MN arising from clastogenic and aneugenic effects and polymorphisms of genes implicated in DNA repair, chromosome segregation, xenobiotic metabolism (activation/detoxification), and folate metabolism. Although it is clear that MN induction can be affected by genetic polymorphisms in various genes involved in DNA repair pathways, xenobiotic metabolism and folate metabolism, more and large-scale studies are required to better understand MN formation driven by genetic polymorphisms, especially for aneuploidy-related genetic polymorphisms.