Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (rs138213197" genes_norm="10481">G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele.
In the present study, carriers of the rare G84E variant in HOXB13 were both younger at the time of diagnosis and more likely to have a family history of prostate cancer compared with homozygotes for the wild-type allele.
Recent genetic epidemiologic studies identified a germline mutation in the homeobox transcription factor, HOXB13G84E, which is associated with markedly increased risk for prostate cancer, particularly early-onset hereditary prostate cancer.
Together, our results suggest that rs339331 affects prostate cancer risk by altering RFX6 expression through a functional interaction with the prostate cancer susceptibility gene HOXB13.
Then, 25 studies including 51,390 cases and 93,867 controls were included, and there was significant association between HOXB13p.Gly84Glu mutation and overall cancer risk (OR = 2.872, 95% CI = 2.121-3.888, P < 0.001), particularly in prostate cancer (OR = 3.248, 95% CI = 2.313-4.560, P < 0.001), while no association was found in breast (OR = 1.424, 95% CI = 0.776-2.613, P = 0.253) and colorectal cancers (OR = 2.070, 95% CI = 0.485-8.841, P = 0.326).
We found that the polygenic PrCa risk score (PR score), calculated using the 71 known single-nucleotide polymorphisms (SNPs) associated with PrCa and the HOXB13G84E variant act multiplicatively on PrCa risk.
For example, a recent study suggested that one cannot adequately impute the HOXB13G84E mutation associated with prostate cancer risk (carrier frequency of 0.0034 in European ancestry participants in the 1000 Genomes Project).
Most notably, HOXB13 and BRCA2 mutations have been consistently shown to increase prostate cancer risk, and are more commonly observed among patients diagnosed with early-onset disease.
These data show that combined MYC activation and Pten loss driven by the Hoxb13 regulatory locus synergize to induce genomic instability and aggressive prostate cancer that phenocopies the human disease at the histologic and genomic levels.
Collaborative investigations using next-generation sequencing to identify genetic variants associated with prostate cancer risk have revealed the significance of HOXB13, BRCA 1/2, and DNA repair mutations.
We identified 101 heterozygous carriers of G84E who underwent radical prostatectomy for prostate cancer between 1985 and 2011 and matched these men by race, age and tumor grade to 99 HOXB13 wild-type controls.
This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers.
These results indicate that risk alleles of HOXB13 and common variant SNPs are important components of inherited PCa risk in the Norwegian population, although these factors appear to contribute little to the malignancy's aggressiveness.
Our group recently developed a transgenic murine model of prostate cancer involving prostate-specific Pten deletion and forced expression of MYC under the control of the Hoxb13 promoter.
Association with PCa risk was statistically significant for variants in BRCA2 (P < 0.001, OR = 5.65, 95% CI = 3.55-9.32), HOXB13 (P < 0.001, OR = 4.73, 95% CI = 2.84-8.19), and ATM (P < 0.001, OR = 2.86, 95% CI = 1.63-5.15).
The mail goal of this research was to study the functional role of Circ-ITCH gene in prostate cancer and to illuminate the function role of circ-ITCH gene in prostate cancer by targeting miR-17-5p/HOXB13.