© 2003 by Oxford University Press
© 2003 Oxford University Press
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Shared Genetic Susceptibility to Breast Cancer, Brain Tumors, and Fanconi Anemia
Affiliations of authors: K. Offit, K. Mah, K. Nafa, M. Robson, N. Ellis (Clinical Genetics Service), L. Norton (Breast Cancer Medicine Service), Memorial Sloan-Kettering Cancer Center, New York, NY; O. Levran, S. D. Batish, R. Diotti, A. D. Auerbach, Laboratory of Human Genetics and Hematology, The Rockefeller University, New York; B. Mullaney, A. Deffenbaugh, T. Scholl, Myriad Genetic Laboratories, Inc., Salt Lake City, UT; H. Schneider, H. Hanenberg, Department of Pediatric Oncology, Hematology and Immunology, Heinrich-Heine University Medical Center, Düsseldorf, Germany; V. K. Proud, Division of Medical Genetics, Children’s Hospital of The King’s Daughters, Norfolk, VA.
Correspondence to: Kenneth Offit, MD, MPH, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021 (e-mail: offitk{at}mskcc.org).
ABSTRACT
Fanconi anemia is an inherited disease characterized by bone marrow failure, congenital malformations, and predisposition to cancer. The breast cancer susceptibility gene BRCA2 was recently found to be associated with Fanconi anemia complementation group D1 (FA-D1). We examined four kindreds afflicted with Fanconi anemia for the presence of germline BRCA2 mutations. One kindred, of Ashkenazi Jewish ancestry, had five members who were diagnosed with breast cancer and two cousins who were BRCA2*6174delT/C3069X compound heterozygotes and had Fanconi anemia and brain tumors. In another kindred of Ashkenazi Jewish and Lithuanian Catholic ancestry, a child with Fanconi anemia and a medulloblastoma was a BRCA2*6174delT/886delGT compound heterozygote. Two other kindreds each contained a Fanconi anemia–afflicted child who developed medulloblastoma; one child was of Latin American ancestry and a compound heterozygote for BRCA2*I2490T/ 5301insA and the other was African American and a compound heterozygote for BRCA2*Q3066X/E1308X. Median age of the Fanconi anemia–afflicted children at brain tumor diagnosis was 3.5 years. The co-occurrence of brain tumors, Fanconi anemia, and breast cancer observed in one of these kindreds constitutes a new syndromic association. Individuals who carry a germline BRCA2 mutation and who plan to have children with a partner of Ashkenazi Jewish descent should consider undergoing genetic counseling.
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