title: MDM2 promoter SNP344T>A (rs1196333) status does not affect cancer risk.
abstract: The MDM2 proto-oncogene plays a key role in central cellular processes like growth control and apoptosis, and the gene locus is frequently amplified in sarcomas. Two polymorphisms located in the MDM2 promoter P2 have been shown to affect cancer risk. One of these polymorphisms (SNP309T>G; rs2279744) facilitates Sp1 transcription factor binding to the promoter and is associated with increased cancer risk. In contrast, SNP285G>C (rs117039649), located 24 bp upstream of rs2279744, and in complete linkage disequilibrium with the SNP309G allele, reduces Sp1 recruitment and lowers cancer risk. Thus, fine tuning of MDM2 expression has proven to be of significant importance with respect to tumorigenesis. We assessed the potential functional effects of a third MDM2 promoter P2 polymorphism (SNP344T>A; rs1196333) located on the SNP309T allele. While in silico analyses indicated SNP344A to modulate TFAP2A, SPIB and AP1 transcription factor binding, we found no effect of SNP344 status on MDM2 expression levels. Assessing the frequency of SNP344A in healthy Caucasians (n = 2,954) and patients suffering from ovarian (n = 1,927), breast (n = 1,271), endometrial (n = 895) or prostatic cancer (n = 641), we detected no significant difference in the distribution of this polymorphism between any of these cancer forms and healthy controls (6.1% in healthy controls, and 4.9%, 5.0%, 5.4% and 7.2% in the cancer groups, respectively). In conclusion, our findings provide no evidence indicating that SNP344A may affect MDM2 transcription or cancer risk.
authors.affiliation: Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway. stian.knappskog@med.uib.no
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.forename: Liv B
authors.initials: LB
authors.lastname: Gansmo
authors.forename: Pål
authors.initials: P
authors.lastname: Romundstad
authors.forename: Merete
authors.initials: M
authors.lastname: Bjørnslett
authors.forename: Jone
authors.initials: J
authors.lastname: Trovik
authors.forename: Jan
authors.initials: J
authors.lastname: Sommerfelt-Pettersen
authors.forename: Erik
authors.initials: E
authors.lastname: Løkkevik
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.forename: Anne
authors.initials: A
authors.lastname: Dørum
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
authors.forename: Lars
authors.initials: L
authors.lastname: Vatten
authors.forename: Per E
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D001483:Base Sequence; D019295:Computational Biology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D051736:Proto-Oncogene Proteins c-mdm2