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The Role of Ataxia-Telangiectasia Heterozygotes in Familial Breast Cancer¹

Clinical Genetics Unit, Department of Molecular Medicine, Karolinska Institute [J. C., G. G., P. L., A. L.], and Department of Pathology, Karolinska Hospital [C. R.], S-17176 Stockholm, Sweden

The role of ataxia-telangiectasia (AT) heterozygotes in breast cancer has been controversial. We have found previously an overrepresentation (3.4%) of ATM mutations in a subset of 88 selected breast cancer patients with a family history of breast cancer, leukemia, and lymphoma. This prevalence is comparable to the estimated value (3.8%) from epidemiological study. To further examine the possibility that ATM is correlated to breast cancer, we screened for ATM germ-line mutations in another 100 breast cancer patients with a family history of breast cancer. We used the protein truncating test and found one new germ-line mutation. This figure (1%) is consistent with the observed 0.2–1% carrier frequency for AT. We also studied breast tumors from ATM mutants, and three showed retention of both alleles, whereas the fourth showed loss of the mutant allele. We conclude that the contribution of heterozygous ATM mutations to familial breast cancer is minimal. Even if the ATM gene were causative in these cases, it is not likely to act as a tumor suppressor.

¹ Supported by the Swedish Cancer Society and The Nordic Cancer Union.

² To whom requests for reprints should be addressed, at Department of Molecular Medicine, Karolinska Institute, S-17176 Stockholm, Sweden. Phone: 46-8-51775248; Fax: 46-8-51773620; E-mail: Annika.Lindblom@cmm.ki.se.

Received 12/ 9/97. Revised 2/ 9/98. Accepted 2/17/98.

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