The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies

Cancer Epidemiol Biomarkers Prev. 2015 Sep;24(9):1366-72. doi: 10.1158/1055-9965.EPI-15-0247. Epub 2015 Jun 24.


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.

Impact: The associations between HOXB13 and prostate, leukemia, and bladder suggest that this gene is important in carcinogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Heterozygote
  • Homeodomain Proteins / genetics*
  • Humans
  • Leukemia / genetics*
  • Male
  • Middle Aged
  • Mutation Rate
  • Mutation*
  • Pedigree
  • Prostatic Neoplasms / genetics*
  • Risk Factors
  • Urinary Bladder Neoplasms / genetics*
  • Young Adult


  • HOXB13 protein, human
  • Homeodomain Proteins