Synonymous Polymorphisms in HOXB13 as a Protective Factor for Prostate Cancer.

BACKGROUND

Genomic association and linkage studies, as well as epidemiological data have implicated both the HOXB13 gene and single nucleotide polymorphisms (SNPs) in the development of prostate cancer (PCa). The recent association between the G84E polymorphism in the HOXB13 gene and PCa has been shown to result in a more aggressive cancer with an earlier onset of the disease. We examined the frequency of this mutation and other recurrent HOXB13 SNPs in patients with PCa and those with benign prostatic hyperplasia (BPH) or no cancer.

METHODS

Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed on exons 1 and 2 of HOXB13 gene, followed by bidirectional Sanger Sequencing on peripheral blood from 232 PCa (age 46-92) and 110 BPH (age 45-84) patients. Statistical analysis was used to correlate between recurrent SNPs and PCa.

RESULTS

The G84E mutation was found at a low frequency in randomly selected PCa and BPH (both 0.9%). Two recurrent, synonymous SNPs, rs8556 and rs900627, were also detected. rs8556 was detected in 48 PCa (20.7%) and 26 BPH (23.6%) subjects; rs9900627was detected in 27 PCa (11.6%) and 19 BPH (17.3%) subjects. Having both rs8556 and rs9900627 or being homozygous for either one was associated with being 2.9 times less likely to develop PCa (p=0.05).

CONCLUSIONS

Although a larger study in order to confirm our findings, our data suggests a significant negative correlation between two SNPs, rs8556 and rs9900627, and the presence of PCa.