title: Vitamin K epoxide reductase expression and prostate cancer risk.
abstract: Increasing evidence has demonstrated that men taking the anticoagulant warfarin have a lower risk of developing prostate cancer. This phenomenon is not observed in other cancers. We sought to determine if the target of warfarin, vitamin K epoxide reductase (VKOR), is expressed in benign and cancerous prostate tissues and if a functional single nucleotide polymorphism (SNP) in the VKOR gene is associated with prostate cancer risk.
  
  
  
  The expression of VKOR was quantified by immunohistochemistry in an institutional series of 54 radical prostatectomy samples and metastatic biopsies, as well as in 40 other cancers and matched benign tissues on a tissue microarray. Genotyping of SNP rs2359612 was performed in a prospective series of 57 patients.
  
  
  
  VKOR is highly expressed in benign human prostate epithelial cells but is not expressed or expressed at very low levels in cancerous cells. This expression pattern is unique to prostate cancer. Additionally, the proportion of the carrier C allele of rs2359612 in the patients with prostate cancer was significantly higher than in the population, suggesting an association between this allele and the risk of having a diagnosis of prostate cancer.
  
  
  
  The expression of VKOR in benign prostate epithelial cells, along with the association between a functional VKOR SNP and prostate cancer risk, suggests a possible role for VKOR in mediating the effect of warfarin on prostate cancer risk. Larger multi-institutional cohort studies are warranted, as are molecular studies on the role of VKOR in prostate cancer development.
authors.affiliation: Department of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.
authors.forename: Ben Yi
authors.initials: BY
authors.lastname: Tew
authors.affiliation: Department of Medical Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: Department of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.
authors.forename: Miaoling
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Pathology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.
authors.forename: Tommy
authors.initials: T
authors.lastname: Tong
authors.affiliation: Department of Pathology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Department of Biostatistics, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.
authors.forename: Xueli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Population Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.affiliation: Department of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA. Electronic address: jjones@coh.org.
authors.forename: Jeremy O
authors.initials: JO
authors.lastname: Jones
mesh_terms: D000368:Aged; D000483:Alleles; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001706:Biopsy; D060005:Genotyping Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control / Q000601:surgery; D046888:Tissue Array Analysis; D064417:Vitamin K Epoxide Reductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014859:Warfarin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: Prostate cancer; Vitamin K epoxide reductase; Warfarin