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High Frequency of Germ-Line BRCA2 Mutations among Hungarian Male Breast Cancer Patients without Family History¹

Department of Molecular Biology, National Institute of Oncology, H-1525 Budapest, Hungary [B. C., N. U., Z. S., I. B, E. O.], and Strangeways Research Laboratories, Cambridge CB1 8RN, United Kingdom [S. R., B. P.]

To determine the contribution of BRCA1 and BRCA2 mutations to the pathogenesis of male breast cancer in Hungary, the country with the highest male breast cancer mortality rates in continental Europe, a series of 18 male breast cancer patients and three patients with gynecomastia was analyzed for germ-line mutations in both BRCA1 and BRCA2. Although no germ-line BRCA1 mutation was observed, 6 of the 18 male breast cancer cases (33%) carried truncating mutations in the BRCA2 gene. Unexpectedly, none of them reported a family history for breast/ovarian cancer. Four of six truncating mutations were novel, and two mutations were recurrent. Four patients (22%) had a family history of breast/ovarian cancer in at least one first- or second-degree relative; however, no BRCA2 mutation was identified among them. No mutation was identified in either of the genes in the gynecomastias. These results provide evidence for a strong genetic component of male breast cancer in Hungary.

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