title: The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian-but not endometrial cancer.
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.
authors: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors: Liv B
authors: LB
authors: Gansmo
authors: Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Merete
authors: M
authors: Bjørnslett
authors: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Center for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Mari Kyllesø
authors: MK
authors: Halle
authors: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Center for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Helga B
authors: HB
authors: Salvesen
authors: Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
authors: Anne
authors: A
authors: Dørum
authors: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors: Einar
authors: E
authors: Birkeland
authors: Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors: Kristian
authors: K
authors: Hveem
authors: Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors: Pål
authors: P
authors: Romundstad
authors: Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors: Lars
authors: L
authors: Vatten
authors: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors: Per Eystein
authors: PE
authors: Lønning
authors: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway. stian.knappskog@med.uib.no.|Department of Oncology, Haukeland University Hospital, Bergen, Norway. stian.knappskog@med.uib.no.
authors: Stian
authors: S
authors: Knappskog
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D018262:Adenocarcinoma, Clear Cell / Q000453:epidemiology / Q000235:genetics; D002288:Adenocarcinoma, Mucinous / Q000453:epidemiology / Q000235:genetics; D000483:Alleles; D018269:Carcinoma, Endometrioid / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D018284:Cystadenocarcinoma, Serous / Q000453:epidemiology / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D009664:Norway / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins
keywords: Cancer risk; Endometrial cancer; MDM4; Ovarian cancer; SNP34091