Molecular epidemiology of DNA repair and cancer susceptibility- a review of population-based studies
The role of DNA repair in the etiology of cancer has been well illustrated in several hereditary syndromes, in which an inherited defect in DNA repair is associated with an extraordinarily high incidence of cancer. However, such an association between an inherited DNA repair defect and the risk of cancer has not been apparent in the general population. In the past 10 years, there has been a growing body of literature that addressed this important research question at the population level. Several assays that measure DNA repair phenotypes (e.g. transfection-based host-cell reactivation, expression of genes and proteins, and cytogenetics, etc.) have been applied to population-based studies. It has been demonstrated that a suboptimal DNA repair capacity for removing DNA damage induced by ultraviolet light and benzo[a]pyrene diol epoxide, two-well known environmental carcinogens, is associated with an increased risk of skin cancer (e.g. melanoma and non-melanoma skin cancers) and tobacco-related cancers (e.g. lung and head and neck cancers), respectively. More recently, the completion of the Human Genome Project and the initiation of the Environmental Genome Project have led to the discovery of numerous single nucleotide polymorphisms in DNA repair genes, followed by a wave of association studies, for cancer in particular. Published data appear to have established a genetic basis for a suboptimal repair phenotype in the general population and provide a rationale for future genetic screening for at-risk populations who can be targeted for the primary prevention of cancer.
