Purpose: Long-term survivors of Hodgkin's disease who received mantle-field irradiation at a young age have a strongly increased risk of developing breast cancer. The purpose of this study was to investigate whether this increased risk was substantially greater among women heterozygous for a germline 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 frame of the ATM gene was analysed for the presence of germline mutations using the protein truncation test and two mutation-specific tests, followed by genomic sequencing.
Results: No A-T disease causing germline mutations were found in these selected Hodgkin patients. However, several alternative splicing events were detected 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 following Hodgkin's disease.