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Open Access 01-08-2016 | Original Article

The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancer

Authors: Liv B. Gansmo, Merete Bjørnslett, Mari Kyllesø Halle, Helga B. Salvesen, Anne Dørum, Einar Birkeland, Kristian Hveem, Pål Romundstad, Lars Vatten, Per Eystein Lønning, Stian Knappskog

Published in: Tumor Biology | Issue 8/2016

Abstract

The MDM4 protein (also known as MDMX or HDMX) is a negative regulator of p53, not only by direct interaction but also through its interaction with MDM2. Further, MDM4 overexpression and amplification have been observed in several cancer forms. Recently, a single nucleotide polymorphism (SNP) in the 3’ untranslated region of the MDM4 gene, SNP34091A > C (rs4245739) was reported to alter MDM4 messenger RNA (mRNA) stability by modulating a microRNA binding site, thereby leading to decreased MDM4 levels. In this case-control study, we aimed to evaluate the possible association between MDM4 SNP34091 status and cancer risk by comparing the genotype frequencies in large hospital-based cohorts of endometrial- (n = 1404) and ovarian (n = 1385) cancer patients with healthy female controls (n = 1870). Genotype frequencies were compared by odds ratio (OR) estimates and Fisher exact tests. We found that individuals harboring the MDM4 SNP34091AC/CC genotypes had a significantly elevated risk for serous ovarian cancer (SOC) in general and high-grade serous ovarian cancer (HGSOC) in particular (SOC: OR = 1.18., 95 % CI = 1.01–1.39; HGSOC: OR = 1.25, CI = 1.02–1.53). No association between SNP34091 genotypes and endometrial cancer risk was observed. Our data indicate the MDM4 SNP34091AC/CC genotypes to be associated with an elevated risk for SOC and in particular the HGSOC type.

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Title: The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancer
Authors: Liv B. Gansmo
Merete Bjørnslett
Mari Kyllesø Halle
Helga B. Salvesen
Anne Dørum
Einar Birkeland
Kristian Hveem
Pål Romundstad
Lars Vatten
Per Eystein Lønning
Stian Knappskog
Publication date: 01-08-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 8/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-016-4940-2

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