Markers of DNA repair and susceptibility to cancer in humans: An epidemiologic review

DNA repair is a system of defenses designed to protect the integrity of the genome. Deficiencies in this system likely lead to the development of canc er. The epidemiology of DNA repair capacity and of its effect on cancer sus ceptibility in humans is, therefore, an important area of investigation, We have summarized all of the published epidemiologic studies on DNA repair i n human cancer through 1998 (n = 64) that addressed the association of canc er susceptibility with a putative defect in DNA repair capacity. We have co nsidered study design, subject characteristics, potential biases, confoundi ng variables, and sources of technical variability. Assays of DNA repair ca pacity used, to date, can be broadly grouped into five categories: 1) tests based on DNA damage induced with chemicals or physical agents, such as the mutagen sensitivity assay, the G(2)-radiation assay, induced micronuclei, and the Comet assay; 2) indirect tests of DNA repair, such as unscheduled D NA synthesis; 3) tests based on more direct measures of repair kinetics, su ch as the host cell reactivation assay; 4) measures of genetic variation as sociated with DNA repair; and 5) combinations of more than one category of assay. The use of such tests in human populations yielded positive and cons istent associations between DNA repair capacity and cancer occurrence (with odds ratios in the range of 1.4-75.3, with the majority of values between 2 and 10), However, the studies that we have reviewed have limitations, inc luding small sample size, "convenience" controls, the use of cells differen t from the target organ, and the use of mutagens that do not occur in the n atural environment. The evolving ability to study polymorphisms in DNA repa ir genes may contribute to new understandings about the mechanisms of DNA r epair and the way in which DNA repair capacity affects the development of c ancer.