Cellular responses to radiation and risk of breast cancer

Mutations in the ataxia telangiectasia gene (ATM) result in an abnormal p53-mediated cellular response to DNA damage produced by ionising radiation. This deficiency is believed to contribute to the radiosensitivity and high cancer risk seen in ataxia telangiectasia (AT) patients and AT heterozygotes. Epidemiological studies have demonstrated that relatives of AT patients are particularly predisposed to breast cancer. This observation, together with the finding that a relatively high proportion of breast cancer patients display an abnormal severe reaction of normal tissues following radiotherapy, has led to the suggestion that AT heterozygosity plays a role in radiosensitivity and breast cancer development. The cloning of the ATM gene has allowed this possibility to be examined at the molecular level. The studies reported to date remain inconclusive, with the number of AT heterozygotes being found in radiosensitive breast cancer patients being less than would be expected based on the family studies. The potential role of several other recently identified genes which are involved in the cellular DNA damage response to ionising radiation and which could also play a role in radiosensitivity and breast cancer development are reviewed. (C) 1999 Elsevier Science Ltd. All rights reserved.