Effect of aging on DNA repair and skin carcinogenesis: a minireview of population-based studies

In the general population, the risk of developing sunlight-induced skin cancer increases as age increases. During the aging process, many biologic factors contribute to the increased risk of developing cancer, including increasing cumulative carcinogenic exposure and increased cellular susceptibility to DNA damage induced by carcinogens. The latter is probably due to an age-related decrease in cellular DNA repair capacity (DRC). Secondary to this decrease in DNA damage repair associated with aging, oncogene activation and amplification also increase, as does the frequency of defects in tumor suppressor genes. All these factors lead to carcinogenesis. Population studies using peripheral blood lymphocytes, transformed lymphoblastoid cells, and primary skin fibroblasts have shown that human DRC decreases with increasing age. The decrease in DRC is also correlated with an increased mutation rate. Reduced DRC may thus be one of the underlying biologic mechanisms for the age-related increase in risk of skin cancer. Therefore, it is important to take the effect of age on DNA repair into account in population studies of DNA repair and skin cancer risk.