title: The single nucleotide polymorphism IVS1+309 in mouse double minute 2 does not affect risk of familial breast cancer.
abstract: 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.
authors.affiliation: Department of Molecular Genetic Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. s.wilkening@dkfz.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilkening
authors.forename: Justo Lorenzo
authors.initials: JL
authors.lastname: Bermejo
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klaes
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002453:Cell Cycle; D002470:Cell Survival; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53
chemical_list: D016159:Tumor Suppressor Protein p53; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2