Markers of dna repair and susceptibility to cancer in humans: an epidemiologic review
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REVIEWMarkers of DNA Repair and Susceptibility to Cancer in Humans: an Epidemiologic Review
Marianne Berwick, Paolo Vineis
At least some of such interindividual difference is likely to have a genetic origin. A number of epidemiologic studies have been conducted to compare measures of DNA repair capacity between cancer case subjects and healthy control subjects to assess the role of repair in the development of human cancer. Such studies have used a variety of measures of DNA repair capacity. However, DNA repair capacity is extremely complex; at this time, the current assays do not measure specific aspects of repair but rather assess more global effects. Most assays are based on an approach that compares induced DNA damage to circulating lymphocytes from subjects with cancer with induced DNA damage to circulating lymphocytes from subjects without cancer with quantitation of subsequent “repair” in both groups. Damage is usually delivered in the form of a “pulse” of carcinogen applied to cell culture (e.g., -rays, UV radiation, benzo[a]pyrene diol epoxide [BPDE], or hydrogen peroxide [H2O2]) or to fresh or cryopreserved lymphocytes. A period of time is allowed to elapse for repair to occur, and then damage is measured in a variety of ways (e.g., as unrepaired single- or double-strand breaks or the rate of incorporation of a radioisotope). We have attempted a formal evaluation of the published studies of DNA repair capacity in the etiology of human cancer and have considered their design, methods, and results. In addition, we have assessed the results and the limitations of such studies. We use the term “DNA repair capacity” to describe a variety of different techniques and manifestations, not all of which are necessarily a direct expression of actual repair of DNA damage but are often a measure of unrepaired DNA damage.
DNA repair is a system of defenses designed to protect the integrity of the genome. Deficiencies in this system likely lead to the development