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BJU Int. 2016 Oct;118(4):646-53. doi: 10.1111/bju.13416. Epub 2016 Feb 12.

Prevalence of the HOXB13 G84E mutation in Danish men undergoing radical prostatectomy and its correlations with prostate cancer risk and aggressiveness.

Author information

1
Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
2
Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
3
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
4
Research Unit for General Practice and Research Centre for Cancer Diagnosis in Primary Care, Aarhus University, Aarhus, Denmark.
5
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. kdso@clin.au.dk.

Abstract

OBJECTIVES:

To determine the prevalence of the HOXB13 G84E mutation (rs138213197) in Danish men with or without prostate cancer (PCa) and to investigate possible correlations between HOXB13 mutation status and clinicopathological characteristics associated with tumour aggressiveness.

MATERIALS AND METHODS:

We conducted a case-control study including 995 men with PCa (cases) who underwent radical prostatectomy (RP) between 1997 and 2011 at the Department of Urology, Aarhus University Hospital, Denmark. As controls, we used 1622 healthy men with a normal prostate specific antigen (PSA) level.

RESULTS:

The HOXB13 G84E mutation was identified in 0.49% of controls and in 2.51% of PCa cases. The mutation was associated with a 5.12-fold increased relative risk (RR) of PCa (95% confidence interval [CI] 2.26-13.38; P = 13 × 10(-6) ). Furthermore, carriers of the risk allele were significantly more likely to have a higher PSA level at diagnosis (mean PSA 19.9 vs 13.6 ng/mL; P = 0.032), a pathological Gleason score ≥7 (83.3 vs 60.9%; P = 0.032), and positive surgical margins (56.0 vs 28.5%; P = 0.006) than non-carriers. Risk allele carriers were also more likely to have aggressive disease (54.2 vs 28.6%; P = 0.011), as defined by a preoperative PSA ≥20 ng/mL, pathological Gleason score ≥ (4+3) and/or presence of regional/distant disease. At a mean follow-up of 7 months, we found no significant association between HOXB13 mutation status and biochemical recurrence in this cohort of men who underwent RP.

CONCLUSIONS:

This is the first study to investigate the HOXB13 G84E mutation in Danish men. The mutation was detected in 0.49% of controls and in 2.51% of cases, and was associated with 5.12-fold increased RR of being diagnosed with PCa. In our RP cohort, HOXB13 mutation carriers were more likely to develop aggressive PCa. Further studies are needed to assess the potential of HOXB13 for future targeted screening approaches.

KEYWORDS:

G84E mutation; HOXB13; cancer risk; prostate; prostate cancer; prostate cancer aggressiveness; prostate neoplasms

PMID:
26779768
DOI:
10.1111/bju.13416
[Indexed for MEDLINE]
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