title: The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies.
abstract: BACKGROUND
  A rare nonconservative substitution (G84E) in the HOXB13 gene has been shown to be associated with risk of prostate cancer. DNA samples from male patients included in the Mayo Clinic Biobank (MCB) were genotyped to determine the frequency of the G84E mutation and its association with various cancers.
  
  
  METHODS
  Subjects were genotyped using a custom TaqMan (Applied Biosystems) assay for G84E (rs138213197). In addition to donating a blood specimen, all MCB participants completed a baseline questionnaire to collect information on medical history and family history of cancer.
  
  
  RESULTS
  Forty-nine of 9,012 male patients were carriers of G84E (0.5%). Thirty-one percent (n = 2,595) of participants had been diagnosed with cancer, including 51.1% of G84E carriers compared with just 30.6% of noncarriers (P = 0.004). G84E was most frequently observed among men with prostate cancer compared with men without cancer (P < 0.0001). However, the mutation was also more commonly observed in men with bladder cancer (P = 0.06) and leukemia (P = 0.01). G84E carriers were more likely to have a positive family history of prostate cancer in a first-degree relative compared to noncarriers (36.2% vs. 16.0%, P = 0.0003).
  
  
  CONCLUSIONS
  Our study confirms the association between the HOXB13 G84E variant and prostate cancer and suggests a novel association between G84E and leukemia and a suggestive association with bladder cancer. Future investigation is warranted to confirm these associations in order to improve our understanding of the role of germline HOXB13 mutations in human cancer.
  
  
  CONCLUSIONS
  The associations between HOXB13 and prostate, leukemia, and bladder suggest that this gene is important in carcinogenesis.
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan. Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. dimmerj@karmanos.org.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Beebe-Dimmer
authors.affiliation: Department of Health Science Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hathcock
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan. Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Yee
authors.affiliation: Departments of Internal Medicine and Urology, University of Michigan School of Medicine, Ann Arbor, Michigan. University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Okoth
authors.affiliation: Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Ewing
authors.affiliation: Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.affiliation: Departments of Internal Medicine and Urology, University of Michigan School of Medicine, Ann Arbor, Michigan. University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cooney
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins