title: MDM4 SNP34091 (rs4245739) and its effect on breast-, colon-, lung-, and prostate cancer risk.
abstract: The MDM4 protein plays an important part in the negative regulation of the tumor suppressor p53 through its interaction with MDM2. In line with this, MDM4 amplification has been observed in several tumor forms. A polymorphism (rs4245739 A>C; SNP34091) in the MDM4 3' untranslated region has been reported to create a target site for hsa-miR-191, resulting in decreased MDM4 mRNA levels. In this population-based case-control study, we examined the potential association between MDM4 SNP34091, alone and in combination with the MDM2 SNP309T>G (rs2279744), and the risk of breast-, colon-, lung-, and prostate cancer in Norway. SNP34091 was genotyped in 7,079 cancer patients as well as in 3,747 gender- and age-matched healthy controls. MDM4 SNP34091C was not associated with risk for any of the tumor forms examined, except for a marginally significant association with reduced risk for breast cancer in a recessive model (OR = 0.77: 95% CI = 0.59-0.99). Stratifying according to MDM2 SNP309 status, we observed a reduced risk for breast cancer related to MDM4 SNP34091CC among individuals harboring the MDM2 SNP309GG genotype (OR = 0.41; 95% CI = 0.21-0.82). We conclude, MDM4 SNP34091 status to be associated with reduced risk of breast cancer, in particular in individuals carrying the MDM2 SNP309GG genotype, but not to be associated with either lung-, colon- or prostate cancer.
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Liv B
authors.initials: LB
authors.lastname: Gansmo
authors.affiliation: Faculty of Medicine, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Romundstad
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Birkeland
authors.affiliation: Faculty of Medicine, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
authors.affiliation: Faculty of Medicine, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Vatten
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011485:Protein Binding; D055503:Protein Multimerization; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Cancer risk; MDM4; SNP309; SNP34091; population based