Increased risk of breast cancer following irradiation for Hodgkin's disease is not a result of ATM germline mutations

Purpose: Long-term survivors of Hodgkin's disease who received mantle-field irradiation at a young age have a strongly increased risk of developing br east cancer. The purpose of this study was to investigate whether this incr eased risk was substantially greater among women heterozygous for a germlin e mutation in the ataxia-telangiectasia gene (ATM). Materials and methods: Thirty-two patients were selected who had developed breast cancer at least 10 years following irradiation for Hodgkin's disease before the age of 45 years. In these patients, the complete open reading f rame of the ATM gene was analysed for the presence of germline mutations us ing the protein truncation test and two mutation-specific tests, followed b y genomic sequencing. Results: No A-T disease causing germline mutations were found in these sele cted Hodgkin patients. However, several alternative splicing events were de tected which might influence protein expression levels. Conclusions: The data suggest that truncating mutations in the ATM gene are not a major component underlying the increased risk of breast cancer follo wing Hodgkin's disease.