Assessment of genetic damage in healthy and diseased tissue

DNA, along with other cellular components, is under constant attack by chemical, physical, and infectious agents present in the human environment, as well as by reactive metabolites generated by physiological processes. Mutations occur as the consequence of this damage, but may also be caused by improper DNA repair of alterations occurring during normal DNA replication and transcription. Genetic damage can occur at the level of the gene (e.g. point mutations, insertions, and deletions) or at the level of the chromosome (e.g. aneuploidy, translocations). Further, mutations can also take place in mitochondrial DNA. Another form of DNA modification is epigenetic methylation of CpG islands, which affects the dynamics of chromatin as well as the expression of a large panel of genes. Recent technical advances have improved the capacity to detect and quantify genetic and epigenetic changes. This chapter summarizes current knowledge on mechanisms of DNA damage and mutagenesis, laying out the concepts for interpreting mutations as biomarkers in investigating the causes and consequences of cancer. It also outlines both established and novel methods for detecting genetic and epigenetic changes in normal and diseased tissues, and then discusses their application in the realm of molecular epidemiology.