Cancer is a disease of altered gene expression involving a complex array of epigenetic events, gene mutation, chromosome rearrangements and altered chromosome number. The coincidence of genotoxic events with the induction of cancer has fueled great interest in molecular/cytogenetic epidemiological studies aimed at linking polymorphisms in genes for DNA repair and carcinogen metabolism and biomarkers of DNA/chromosome damage with cancer risk. These studies are now being expanded to include the role of dietary factors that are known to be important in DNA metabolism and repair such as folic acid, vitamin B12 and zinc. The use of DNA damage biomarkers as a surrogate for cancer would greatly facilitate our capacity to identify the most important risk factors for cancer however these biomarkers need validation. The Nordic and Italian prospective cohort studies have confirmed that elevated rates of chromosome aberrations in lymphocytes are predictive of cancer risk and similar studies are now underway to validate other biomarkers such as the micronucleus assay which are more practical to apply in the larger population setting. Validation of these biomarkers requires a thorough understanding of the importance of methodological, demographic, environmental and dietary variables and the ongoing HUMN project is a good example how this can be achieved for the micronucleus assay. The capacity to study human populations has opened up new opportunities to define acceptable DNA damage rates and to establish recommended dietary allowances for genomic stability. Controlling DNA damage rate to its possible minimum is likely to have an important impact in preventing cancer and other DNA damage-related degenerative diseases including ageing.