title: Mutation analysis of the MSMB gene in familial prostate cancer.
abstract: BACKGROUND
  MSMB, a gene coding for beta-microseminoprotein, has been identified as a candidate susceptibility gene for prostate cancer (PrCa) in two genome-wide association studies (GWAS). SNP rs10993994 is 2 bp upstream of the transcription initiation site of MSMB and was identified as an associated PrCa risk variant. The MSMB protein is underexpressed in PrCa and it was previously proposed to be an independent marker for the recurrence of cancer after radical prostatectomy.
  
  
  METHODS
  In this study, the coding region of this gene and 1500 bp upstream of the 5'UTR has been sequenced in germline DNA in 192 PrCa patients with family history. To evaluate the possible effects of these variants we used in silico analysis.
  
  
  RESULTS
  No deleterious mutations were identified, however, nine new sequence variants were found, most of these in the promoter and 5'UTR region. In silico analysis suggests that four of these SNPs are likely to have some effect on gene expression either by affecting ubiquitous or prostate-specific transcription factor (TF)-binding sites or modifying splicing efficiency.
  
  
  CONCLUSIONS
  We conclude that MSMB is unlikely to be a familial PrCa gene and propose that the high-risk alleles of the SNPs in the 5'UTR effect PrCa risk by modifying MSMB gene expression in response to hormones in a tissue-specific manner.
authors.affiliation: Translational Cancer Genetics Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. zsofia.kote-jarai@icr.ac.uk
authors.forename: Z
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: D
authors.initials: D
authors.lastname: Leongamornlert
authors.forename: M
authors.initials: M
authors.lastname: Tymrakiewicz
authors.forename: H
authors.initials: H
authors.lastname: Field
authors.forename: M
authors.initials: M
authors.lastname: Guy
authors.forename: A A
authors.initials: AA
authors.lastname: Al Olama
authors.forename: J
authors.initials: J
authors.lastname: Morrison
authors.forename: L
authors.initials: L
authors.lastname: O'Brien
authors.forename: R
authors.initials: R
authors.lastname: Wilkinson
authors.forename: A
authors.initials: A
authors.lastname: Hall
authors.forename: E
authors.initials: E
authors.lastname: Sawyer
authors.forename: K
authors.initials: K
authors.lastname: Muir
authors.forename: F
authors.initials: F
authors.lastname: Hamdy
authors.forename: J
authors.initials: J
authors.lastname: Donovan
authors.forename: D
authors.initials: D
authors.lastname: Neal
authors.forename: D
authors.initials: D
authors.lastname: Easton
authors.forename: R
authors.initials: R
authors.lastname: Eeles
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D029584:Prostatic Secretory Proteins / Q000235:genetics*
chemical_list: D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein