An Expressed Retrogene of the Master Embryonic Stem Cell Gene POU5F1 Is Associated With Prostate Cancer Susceptibility

Am J Hum Genet. 2014 Mar 6;94(3):395-404. doi: 10.1016/j.ajhg.2014.01.019. Epub 2014 Feb 27.


Genetic association studies of prostate and other cancers have identified a major risk locus at chromosome 8q24. Several independent risk variants at this locus alter transcriptional regulatory elements, but an affected gene and mechanism for cancer predisposition have remained elusive. The retrogene POU5F1B within the locus has a preserved open reading frame encoding a homolog of the master embryonic stem cell transcription factor Oct4. We find that 8q24 risk alleles are expression quantitative trait loci correlated with reduced expression of POU5F1B in prostate tissue and that predicted deleterious POU5F1B missense variants are also associated with risk of transformation. POU5F1 is known to be self-regulated by the encoded Oct4 transcription factor. We further observe that POU5F1 expression is directly correlated with POU5F1B expression. Our results suggest that a pathway critical to self-renewal of embryonic stem cells may also have a role in the origin of cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic
  • Databases, Genetic
  • Embryonic Stem Cells / cytology
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism*
  • Open Reading Frames
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism*
  • Quantitative Trait Loci
  • Risk
  • Sequence Analysis, DNA
  • Transcription, Genetic
  • Young Adult


  • Octamer Transcription Factor-3
  • POU5F1 protein, human