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The Single Nucleotide Polymorphism IVS1+309 in Mouse Double Minute 2 Does Not Affect Risk of Familial Breast Cancer

¹ Department of Molecular Genetic Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum); ² Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; ³ Department of Gynaecology and Obstetrics, Division for Tumor Genetics, Klinikum rechts der Isar; ⁴ Department of Gynaecology and Obstetrics at the Ludwig-Maximilians-University, Munich, Germany; ⁵ Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Württemberg-Hessia, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany; ⁶ Division of Molecular Gynaeco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center University of Cologne, Cologne, Germany; and ⁷ Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden

Requests for reprints: Stefan Wilkening, Department of Molecular Genetic Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. Phone: 49-6221-421803; Fax: 49-6221-421810; E-mail: s.wilkening{at}dkfz.de.

The mouse double minute 2 (MDM2) oncoprotein promotes cell survival and cell cycle progression by inhibiting the p53 tumor suppressor protein. Further, MDM2 overexpression can inhibit DNA double-strand break repair in a p53-independent manner. Recently, it was shown that a single nucleotide polymorphism (SNP) in the MDM2 promoter was associated with an accelerated tumor formation in individuals with a p53 mutation. The present case-control study investigated the association of this SNP (IVS1+309) with the risk and the age of onset of familial breast cancer in patients with unknown p53 mutation status. Data from 549 women affected by familial breast cancer and 1,065 healthy controls were analyzed. The cases did not carry BRCA1/2 mutations. Cases and controls showed a similar genotype distribution and the SNP did not seem to modify the age of onset of familial breast cancer. The data were also examined taking into account the presence of any additional cancer after breast cancer and the family history of cases; however, no association was found. These results suggest that the SNP IVS1+309 alone affects neither the risk nor the age of onset of heritable breast cancer. (Cancer Res 2006; 66(2): 646-8)

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