Complete or partial inability to sense and repair DNA damage increases the risk of developing cancer. The ataxia telangiectasia mutated (ATM) protein kinase has a crucial role in response to DNA double-strand breaks. Hereditary mutations in the ATM gene are the cause of a rare genomic instability syndrome ataxia telangiectasia (AT) characterized, among others, by elevated cancer risk. Although clear in homozygotes, numerous studies have failed to find a link between heterozygotes and cancer. However, there is increasing evidence that ATM heterozygotes have an increased risk of developing breast cancer. First, epidemiological studies conferred an increased risk of breast cancer among AT relatives. Second, in vitro studies of heterozygous cells provide strong evidence of hyperradiosensitivity. Third, some clinical studies found an increased frequency of ATM mutations among high-risk breast cancer families.

Department of Biochemistry and Experimental Oncology 1st Faculty of Medicine Charles University Prague Czech Republic

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