title: HOXB13 mutation and prostate cancer: studies of siblings and aggressive disease.
abstract: BACKGROUND
  Recent work detected for the first time a high-risk prostate cancer mutation, in homeobox B13 (HOXB13) among European-Americans.
  
  
  METHODS
  We further evaluated this G84E missense mutation (rs138213197) in two genetic association studies of prostate cancer: a family-based study of brothers and a case-control study of more aggressive disease (N = 2,665 total). We then calculated overall impact of this mutation by pooling all published studies of European-Americans.
  
  
  RESULTS
  In our studies, the mutation was found exclusively among men with prostate cancer (carrier frequency = 1.48%) or unaffected brothers of cases carrying the mutation (frequency = 0.34%), and carrying the mutation gave an OR for disease = 4.79 (P = 0.01). The G84E mutation was more common among men with an earlier age of onset (≤55 years) or a family history of prostate cancer. We also observed for the first time an African-American case carrying the G84E mutation, although at HOXB13 both of his chromosomes were of European-American ancestry. The pooled analysis also indicated that carrying the G84E mutation results in an almost five-fold increase in risk of prostate cancer (P = 3.5 × 10(-17)), and this risk is even higher among cases with an early age of prostate cancer onset (≤55 years) or a family history of disease: a test of heterogeneity across these strata gives P < 1 × 10(-5).
  
  
  CONCLUSIONS
  The HOXB13 mutation substantially increases risk of early onset, familial prostate cancer in European-American men.
  
  
  CONCLUSIONS
  Testing for the G84E mutation in men with a positive family history may help distinguish those who merit more regular screening for prostate cancer.
authors: Departments of Epidemiology & Biostatistics and Urology, University of California San Francisco, San Francisco, CA 94158, USA. jwitte@ucsf.edu
authors: John S
authors: JS
authors: Witte
authors: Joel
authors: J
authors: Mefford
authors: Sarah J
authors: SJ
authors: Plummer
authors: Jinghua
authors: J
authors: Liu
authors: Iona
authors: I
authors: Cheng
authors: Eric A
authors: EA
authors: Klein
authors: Benjamin A
authors: BA
authors: Rybicki
authors: Graham
authors: G
authors: Casey
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012307:Risk Factors; D035781:Siblings
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; D004247:DNA
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