title: HOXB13 G84E mutation in Finland: population-based analysis of prostate, breast, and colorectal cancer risk.
abstract: BACKGROUND
  A recently identified germline mutation G84E in HOXB13 was shown to increase the risk of prostate cancer. In a family-based analysis by The International Consortium for Prostate Cancer Genetics (ICPCG), the G84E mutation was most prevalent in families from the Nordic countries of Finland (22.4%) and Sweden (8.2%).
  
  
  METHODS
  To further investigate the importance of G84E in the Finns, we determined its frequency in more than 4,000 prostate cancer cases and 5,000 controls. In addition, 986 breast cancer and 442 colorectal cancer (CRC) cases were studied. Genotyping was conducted using TaqMan, MassARRAY iPLEX, and sequencing. Statistical analyses were conducted using Fisher exact test, and overall survival was analyzed using Cox modeling.
  
  
  RESULTS
  The frequency of the G84E mutation was significantly higher among patients with prostate cancer and highest among patients with a family history of the disease, hereditary prostate cancer [8.4% vs. 1.0% in controls; OR 8.8; 95% confidence interval (CI), 4.9-15.7]. The mutation contributed significantly to younger age (≤55 years) at onset and high prostate-specific antigen (PSA; ≥20 ng/mL) at diagnosis. An association with increased prostate cancer risk in patients with prior benign prostate hyperplasia (BPH) diagnosis was also revealed. No statistically significant evidence for a contribution in CRC risk was detected, but a suggestive role for the mutation was observed in familial BRCA1/2-negative breast cancer.
  
  
  CONCLUSIONS
  These findings confirm an increased cancer risk associated with the G84E mutation in the Finnish population, particularly for early-onset prostate cancer and cases with substantially elevated PSA.
  
  
  CONCLUSIONS
  This study confirms the overall importance of the HOXB13 G84E mutation in prostate cancer susceptibility.
authors.affiliation: Johanna Schleutker, Medical Biochemistry and Genetics, Institute of Biomedicine, Kiinamyllynkatu 10, FI-20014 University of Turku, Finland. Johanna.Schleutker@utu.fi
authors.forename: Virpi H
authors.initials: VH
authors.lastname: Laitinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Wahlfors
authors.forename: Leena
authors.initials: L
authors.lastname: Saaristo
authors.forename: Tommi
authors.initials: T
authors.lastname: Rantapero
authors.forename: Liisa M
authors.initials: LM
authors.lastname: Pelttari
authors.forename: Outi
authors.initials: O
authors.lastname: Kilpivaara
authors.forename: Satu-Leena
authors.initials: SL
authors.lastname: Laasanen
authors.forename: Anne
authors.initials: A
authors.lastname: Kallioniemi
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: Lauri
authors.initials: L
authors.lastname: Aaltonen
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
authors.forename: Tapio
authors.initials: T
authors.lastname: Visakorpi
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D004247:DNA / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; D004247:DNA