Germline Mutations of the Ataxia-Telangiectasia Gene, ATM, as a Risk Factor for Radiation-Associated Breast Cancer.

This project is a case-control study designed to determine whether or not the presence of a germline mutation in ATM, the gene responsible for ataxia-telangiectasia, significantly increases the risk of breast cancer after exposure to a defined dose of therapeutic irradiation. The study population will be comprised of women who have developed breast cancer after treatment for Hodgkins Disease. As of the date of this report, 33 such women have received genetic counseling, provided informed consent, and donated a blood specimen for germline ATM testing. Controls will be selected from a cohort of women who have received radiation, but have not developed breast cancer. The identification and counseling of these controls is proceeding. To date, 5 controls have donated a sample for testing. Potential difficulties in accruing sufficient numbers of cases and controls are being resolved by collaboration with other centers with large numbers of cases of Hodgkins Disease andor breast cancer. Screening for deleterious mutations will be performed using protein truncation testing and restriction endonuclease fingerprinting, the methodologies for which are under development. Once mutational analysis is complete, the odds ratio for radiation-induced breast cancer associated with ATM mutations will be calculated using standard methodologies.