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Abstract
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.