Repair of oxidative DNA damage: assessing its contribution to cancer prevention

DNA repair is a crucial factor in maintaining a low steady-state level of oxidative DNA damage and protecting us from cancer. Cancer case-control studies, using indirect assays in which chromosome breakage in lymphocytes is taken as a measure of failure to repair DNA, indicate an association between poor repair and cancer risk, but case-control studies can be misleading. Surprisingly little is known of the variations in repair capacity within healthy human populations. It is likely that differences in repair enzyme activity result from genetic polymorphisms in repair genes, which have been shown, in some cases, to be linked to cancer. There is a need for prospective studies, in which genotype is analysed (for a range of repair and related genes) and repair activity measured before cancer has developed. Using a new method to measure repair in an extract of lymphocytes, based on a modification of the comet assay, we are seeking answers to the following questions: what is the normal range of repair activities in healthy humans; do differences in repair capacity correlate with genetic variations; is low repair capacity associated with a high risk of cancer; how important is DNA repair rate in determining the steady-state level of damage; what is the extent of intra-individual variation; is repair modulated by environmental factors or induced by damage; are there differences in repair capacity between men and women; what is the association of DNA repair with ageing?