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Published in: Familial Cancer 1/2014

01-03-2014 | Short Communication

The MDM2 285G–309G haplotype is associated with an earlier age of tumour onset in patients with Li-Fraumeni syndrome

Authors: Mariette Renaux-Petel, Richard Sesboüé, Stéphanie Baert-Desurmont, Stéphanie Vasseur, Steeve Fourneaux, Emilie Bessenay, Thierry Frébourg, Gaëlle Bougeard

Published in: Familial Cancer | Issue 1/2014

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Abstract

In the Li-Fraumeni syndrome (LFS) resulting from germline TP53 mutations, the MDM2 SNP309G allele has been shown to be associated with an earlier age of tumour onset, however the significance of this association is controversial. The 285C variation, also located in the MDM2 promoter, has been shown to reduce the strength of Sp1 binding to MDM2 promoter, antagonizing the effect of the 309G variation. In this study, we investigated the interaction of the MDM2 SNP285 and 309 in a large series of 195 LFS patients. Although we observed a lower mean age of tumour onset in patients with MDM2 SNP309 T/G or G/G genotype (23.1 years) than in patients with T/T genotype (27.3 years), the difference was not statistically significant. In contrast, patients with the 285–309 G–G haplotype develop tumours 5 years earlier than patients harbouring other haplotypes (p = 0.044). This result shows that the MDM2 285–309 G–G is a higher risk haplotype in patients with germline TP53 mutations. This study confirms that the MDM2 309G variation is deleterious when its effect is not neutralized by the 285C variation and illustrates the interfering effects of SNPs located within a gene acting as modifier factor in a Mendelian disease.
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Metadata
Title
The MDM2 285G–309G haplotype is associated with an earlier age of tumour onset in patients with Li-Fraumeni syndrome
Authors
Mariette Renaux-Petel
Richard Sesboüé
Stéphanie Baert-Desurmont
Stéphanie Vasseur
Steeve Fourneaux
Emilie Bessenay
Thierry Frébourg
Gaëlle Bougeard
Publication date
01-03-2014
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 1/2014
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-013-9667-2

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