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

Content Provider	Springer Nature Link
Author	Renaux Petel, Mariette Sesboüé, Richard Baert Desurmont, Stéphanie Vasseur, Stéphanie Fourneaux, Steeve Bessenay, Emilie Frébourg, Thierry Bougeard, Gaëlle
Copyright Year	2013
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.
Starting Page	127
Ending Page	130
Page Count	4
File Format	PDF
ISSN	13899600
Journal	Familial Cancer
Volume Number	13
Issue Number	1
e-ISSN	15737292
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-07-25
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Li-Fraumeni syndrome MDM2 Modifier genes TP53 Cancer Research Human Genetics Epidemiology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Genetics Cancer Research Genetics (clinical) Oncology

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