title: The MDM2 promoter SNP285C/309G haplotype diminishes Sp1 transcription factor binding and reduces risk for breast and ovarian cancer in Caucasians.
abstract: MDM2 plays a key role in modulating p53 function. The MDM2 SNP309T > G promoter polymorphism enhances Sp1 binding and has been linked to cancer risk and young age at diagnosis although with conflicting evidence. We report a second MDM2 promoter polymorphism, SNP285G > C, residing on the SNP309G allele. SNP285C occurs in Caucasians only, where 7.7% (95% CI 7.6%-7.8%) of healthy individuals carry the SNP285C/309G haplotype. In vitro analyses reveals that SNP309G enhances but SNP285C strongly reduces Sp1 promoter binding. Comparing MDM2 promoter status among different cohorts of ovarian (n = 1993) and breast (n = 1973) cancer patients versus healthy controls (n = 3646), SNP285C reduced the risk of both ovarian (OR 0.74; CI 0.58-0.94) and breast cancer (OR 0.79; CI 0.62-1.00) among SNP309G carriers.
authors.affiliation: Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway.
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.forename: Merete
authors.initials: M
authors.lastname: Bjørnslett
authors.forename: Line M
authors.initials: LM
authors.lastname: Myklebust
authors.forename: Petra E A
authors.initials: PE
authors.lastname: Huijts
authors.forename: Maaike P
authors.initials: MP
authors.lastname: Vreeswijk
authors.forename: Hege
authors.initials: H
authors.lastname: Edvardsen
authors.forename: Yongli
authors.initials: Y
authors.lastname: Guo
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Sanna K
authors.initials: SK
authors.lastname: Ylisaukko-Oja
authors.forename: Pia
authors.initials: P
authors.lastname: Alhopuro
authors.forename: Johanna
authors.initials: J
authors.lastname: Arola
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Christi J
authors.initials: CJ
authors.lastname: van Asperen
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Vidar
authors.initials: V
authors.lastname: Staalesen
authors.forename: Ranjan
authors.initials: R
authors.lastname: Chrisanthar
authors.forename: Erik
authors.initials: E
authors.lastname: Løkkevik
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.forename: Camilla
authors.initials: C
authors.lastname: Stoltenberg
authors.forename: Pål
authors.initials: P
authors.lastname: Romundstad
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
authors.forename: Johan R
authors.initials: JR
authors.lastname: Lillehaug
authors.forename: Lars
authors.initials: L
authors.lastname: Vatten
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.forename: Anne
authors.initials: A
authors.lastname: Dørum
authors.forename: Per E
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D044465:White People
chemical_list: D011960:Receptors, Estrogen; D016329:Sp1 Transcription Factor; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2