Prostate cancer and

HOXB13 G84E
• Cancer is a disease caused by the uncontrolled growth of the cells of the
body. This uncontrelled growth is most likely cause by the unactivity of
the P53 tumor suppressor protein, gene that lead the cell to undergo
apoptosis, the natural death of the cell.
• concerning Prostate caner as the name implies is a cancer occuring at the
prostate region, gland possessed only by men. The prostate is a gland
situated between the bladder and the penis of the man.
• After the analysis of 175 pedigrees of families having individuals with prostate
cancer by the University of Michigan Prostate Cancer Genetic Project it has
been showed that prostate cancer was related to a gene in other words, having a
relative having the prostate cancer increase the chance of getting it too.
• After finidng that cancer is linked to the genes the next step was to find where it
was located.
• One of the most intensely investigated regions of the genome for prostate
cancer susceptibility loci is chromosome 17q21-22
• One of the most intensely investigated regions of the genome for prostate
cancer susceptibility loci is chromosome 17q21-22
EXPERIENCES AND RESULTS

• Experience N°1
*Prostate Cancer Genetics Project: men with prostate cancer who had at least one living first- or second degree
relative who also had prostate cancer or those in whom prostate cancer had been diagnosed at an age of 55 years or
less, regardless of family history.
*Johns Hopkins University: families with hereditary prostate cancer each had at least three first-degree relatives
with prostate cancer.
*men who underwent screening for prostate cancer with a negative diagnosis with knowledge of ancestry
* The youngest patient with prostate cancer where selected: 7 African descent, 2 Asian descent, 85 European descent
for their DNA
* Analysis of the DNA specially for the loci was done using MassARRAY system and TaqMan assays.
• Results N°1
*202 genes were on found on the loci of the chromosome 17q21-22
*probands from 4 families were observed to have the same nonsynonymous mutation:
HOXB13.
*cosegregation of the mutation with disease was observed in all 18 affected men in the ‘
families
*knowing the importance of HOXB13 in prostate biology, an other experience was carried to
further characterize this mutation
• Experience N°2
*5083 unrelated case subjects: -1130with early onset or familial prostate cancer from PCGP
-161 with hereditary prostate from JHU
-3499 with localized prostate cancer who were treated
with radical prostatectomy from JHH
-293 treated for advanced prostate cancer from JHH
*1401 unrelated control subjects found negative for prostate cancer during screening
• Results N°2
*men with prostate cancer were significantly more likely to carry the HOXB13 G84E allele (1.4%), than
those without
*the carrier frequency varied as a function of age at diagnosis and family history
*the carrier frequency among those have been early diagnosed (≤55 years of age) and have a positive family
history is 3.1% while in men with only positive family history 1.2% and only early diagnosed 1.0%
*the lowest carrier frequency was observed in men whom prostate cancer was diagnosed after 55 years old
and who didn’t have a family history of the disease
*results were the same for data from Prostate Cancer Genetic Project and Johns Hopkins University
 Discussion
A recurrent mutation, G84E in HOXB13, was found to be associated with prostate cancer risk, in
particular early onset and hereditary prostate cancer.
The HOX genes are a subfamily of the homeobox superfamily of transcription factors characterized by
a highly conserved DNA-binding domain: the homeodomain.
Human have 4 kinds of HOX clusters: HOXA on chrom.7, the HOXB on chrom.17, the HOXC on
chrom.12 , and the HOXD on chrom.2
Their coordinated expression called HOX code is essential fo the pattern formation of the animal body.
Some HOX genes are 3’genes, genes expressed early in anterior and proximal regions
Some HOX genes are 5’genes, expressed lately in posterior and distal regions
The paralogue group 13 of HOX genes are the one influencing the posterior
domains, including the the developing urogenital system in vertebrates.
Hoxb 13 Iis one of the genes that maintains a high expression level into
adulthood in normal prostate and a lesser level in distal colon.
Hoxb13 has been found to be at the same time a tumor suppressor and an
oncogene in prostate cancer and others cancer types.
Hoxb13 physically interacts with the androgen receptors that are really important
in the growth and the regulation of both prostate cancer and prostate biology
 HOXB13
¤Gene encoding transcription factor homeobox B13, that belongs to the
homeobox gene family those genes are very important for vertebrate
embryonic development.
¤Responsible of the sequence-specific transcription factor which is a part of
a developmental regulatory system that provides cells with specific
positional identities on the anterior-posterior axis
¤HOXB13 gene is a gene producing a protein that regulate the transcription
of other genes. It is a kind of homeotic genes ,HOX genes.
 G84E
• Its mutation is known as a factor of increasing the risk of having prostate
cancer .
• That mutation is situated at its 2nd base of its 84th codon
GGA→GAA
This SNP causes the production of glycine instead of glutamic acid.
Researches about Prostate cancer until today haven’t found the real reasosns,
or causes of prostate cancer.
And as HOXB13 G84E was found to have the ability to increase the risk of
having prostate cancer, there is a great probabilty that news gene in relation
with the disease may be found.