In addition to the loss of HOXB13 expression, maintaining AR may be an important step for prostate cancer cells to tolerate the suppressor function of HOXB13.
To confirm this association in a screening setting, we conducted a case-control study and sequenced germline DNA from peripheral leukocytes of 1843 men diagnosed with prostate cancer (case subjects) and 2225 men without prostate cancer (control subjects) for mutations in HOXB13.
We also report results for a previously described HOXB13 variant (rs138213197[T]), confirming it as a prostate cancer risk variant in populations from across Europe.
Results from this study implicated a novel effect of ATRA in inhibition of the growth of AR(-) resistant human prostate cancer cells through alteration of HOXB13 expression as a result of epigenetic modifications.
These results confirm the association of a rare HOXB13 mutation with PC in the general population and suggest that this variant may be associated with features of more aggressive disease.
This study has also shown that the majority of hereditary prostate cancers due to the HOXB13 missense mutation are 'sporadic' in the sense that unselected cases with the missense mutation do not typically report having a family history of prostate cancer.
In conclusion, the G84E mutation of HOXB13, a relatively recent mutation that likely occurred in Northern Europe, significantly increases risk for PCa.
HOXB13G84E was observed in 1.3% of population controls and was strongly associated with prostate cancer risk (CAPS: odds ratio [OR]: 3.4; 95% confidence interval [CI], 2.2-5.4; Stockholm-1: OR: 3.5; 95% CI, 2.4-5.2).
While the HOXB13G84E mutation may be rare, there may be a future role in genetic testing for this mutation after further studies of clinical utility in assessing prostate cancer risk.