Question on HOXB13 pathogenic mutation of p.G84E

[monkey1991]

Has anyone been identified with this pathogenic mutation and if so can you please share any treatment options and outcomes. I am 18 years in as stage 4, former Myers patient. Currently coming off estrogen patch’s after xytiga failure. Thanks

[pjoshea13]

For those wondering what HOXB13 p.G84E is, I have skimmed through the literature.

There have been plenty of studies that have assessed the associated risk of PCa in European & Scandinavian countries. i.e the percentage of population affected (very small) & the increased risk of PCa.

From 2013 [1] (the REDUCE trial):

"A novel rare mutation, homeobox B13 (HOXB13) G84E, was reported to co-segregate with prostate cancer (PCa) in hereditary PCa families and associate with PCa risk in unrelated cases and controls."

"... the G84E mutation of HOXB13, a relatively recent mutation that likely occurred in Northern Europe, significantly increases risk for PCa."

"In Finland, the G84E mutation was estimated to occur in the year 1792" (!!!)

{1792: Dreadful year. French revolution. France's King Louis XVI goes on trial, accused of high treason and crimes against the state.}

Unfortunately, as of 2015:

"The clinical importance of HOXB13 G84E in PrCa management has not been established." [2]

The latest paper [3] (from Poland) makes passing reference to older studies:

"Karlsson et al. showed a higher incidence of G84E in a group of PC men from Sweden than in a national control population collected between 2001 and 2003 (4.6% vs. 1.4%), or in a group of PC men coming only from Stockholm (biopsy-positive patients) than in biopsy-negative controls collected between 2005 and 2007 (4.3% vs. 1.3%) [29]. In this study, the odds ratio (OR) of PC occurrence in G84E carriers was estimated at 7.21 (similarly, in the Breyer et al. study – 7.9, in the Akbari et al. study – 5.8, and in the Storebjerg et al. study – 5.1) [21, 26, 29, 32]. In the study by Kote-Jarai et al. the OR of a PC occurrence in G84E carriers was slightly lower and was estimated at 2.93 (in the Chen et al. study – 3.8) [19, 33]. Except in the Chinese population, where the G84E was not present, all the studies carried thus far have confirmed the significant role of G84E mutation in prostate cancer development [20, 21, 26, 27, 29, 30].

Breyer et al. revealed a 1.9% G84E frequency in men from families with at least one case of prostate cancer, 2.7% in men from families with at least three PC cases, and 1.5% in men from families in which no PC case was detected [26]. Kote-Jarai et al. reported the prostate cancer risk being significantly higher for HOXB13 G84E mutation carriers with a family history of PC (defined as prostate cancer in a first- or second-degree relative at any age) compared with non-carriers, with an OR of 4.7. The frequency of G84E mutation in prostate cancer patients with family history of PC was 2.4% and in those with no family history (defined as lack of PC in a first- or second-degree relative) was two-times lower, at 1.2% [19]. In our study, the G84E frequency in patients from families with HPC (8.0%) was significantly higher than in patients from families which did not fulfil the HPC criteria (1.3%). The association of G84E with the hereditary form of PC was also confirmed by KluŸniak et al. and Ewing et al. [20, 27].

An analysis of the age at PC onset of G84E carriers in our study shows that the presence of this mutation may be associated with older age at PC onset; in 2 of 3 G84E carriers, prostate cancer was diagnosed at age > 60 years (61 and 67 years). There was no statistically significant difference in the mean age at PC diagnosis in G84E carriers and non-carriers (59.7 ±8.01 vs. 60.0 ±6.0, p = 0.93). In contrast, Karlsson et al. observed in a Swedish population a younger mean age at PC diagnosis in G84E carriers than in non-carriers: 62.1 vs. 65.0, respectively; in a Stockholm population: 63.3 vs. 65.9, respectively) [29]. Similarly, Ewing et al. demonstrated the relationship between G84E presence and PC development at a younger age (≤ 55 years of age) and with familial aggregation of this cancer (≥ 2 PC relatives). The mutation was present in 2.2% of men with PC detected before 55 years of age and in 0.8% diagnosed after 55 years of age [20]. Thus, further analysis of the age at PC onset of G84E carriers from the Polish population is needed to elucidate this problem."

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl...

[2] ncbi.nlm.nih.gov/pubmed/255...

[3] termedia.pl/G84E-germline-m...

[Jbooml in reply to pjoshea13]

Its role in GU (prostate) development and homeostasis is being much investigated in it role with MEIS co factoring in early onset metastatic PC. I'm in that demograph being a Finn with early onset. I haven't been tested but I'm a low T etc. It seems all the other hox transcriptional factors are in play in malignancy up and down regulation.

[pjoshea13 in reply to Jbooml]

Thanks. -Patrick

[monkey1991 in reply to pjoshea13]

Thanks, good info

[Hotrod65]

Autosomal Gene identified by Genetics testing and a possible precursor to PC development, but not definitive?, Not a treatment available for specific Hoxb13, but as an overall treatment Regimine for specific cancer identified..hope that is a simpler explanation.

[j-o-h-n]

Hello Rudy... stop monkeying around....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 01/28/2020 6:31 PM EST