African Americans have about one-and-a-half times the incidence and
twice the mortality associated with prostate cancer of European
Americans, and the reasons for this are not clear.
A team of scientists has identified MNX1 as a new oncogene - a gene
than can cause cancer - that is more active in African American prostate
cancer than in European American prostate cancer. The finding suggests
that genetic factors can contribute, at last in part, to the higher
incidence of prostate cancer among African American men compared with
men of other ethnic groups.
‘Genetic factors can contribute to the higher incidence of prostate cancer among African American men compared with men of other ethnic groups.’
The team includes scientists at Baylor
College of Medicine, Third Military Medical University in China, the
Michael E. DeBakey VA Medical Center, and Agilent Technologies India
Pvt. Ltd. The study appeared in Cancer Research
Most scientists think that some of the health disparities among
ethnic groups can be explained by differences in biology. Socio-economic
factors, such as unequal access to healthcare services that make
African American men less likely to receive regular physical
examinations and screening for prostate cancer, may also be involved.
To study the genetic differences between African American prostate
cancer and European American prostate cancer, the scientists took
advantage of the tremendously diverse resources available at the Dan L
Duncan Comprehensive Cancer Center at Baylor, which include one of the
most extensive African American prostate tissue banks.
"We determined the gene expression profiling of African American
prostate cancers," said senior author
Dr. Michael Ittmann, professor of pathology & immunology at Baylor
and the Michael E. DeBakey Department of VA Medical Center, "and compared it with that of normal
prostate tissue. Then, in collaboration with Dr. Chad Creighton,
associate professor of medicine at Baylor and member of the Dan L Duncan
Comprehensive Cancer Center Division of Biostatistics, we compared the
gene expression profiling of African American prostate cancers with that
of European American prostate cancers, which is available in published
"We found 24 genes that were different between the African American
and the European American prostate cancer datasets," said Ittmann. "Some
of the genes were less active in African American prostate cancer, but
we concentrated on those that were more active as they could potentially
be oncogenes. MNX1 was at the top of the list."
MNX1 had been previously described as an oncogene linked to
infantile acute myeloid leukemia, a rare cancer of the bone marrow and
"Our study so far suggested that MNX1 was likely an oncogene in
prostate cancer. The protein the MNX1 gene produces is a transcription
factor; it can turn on gene transcription in other genes, which results
in those genes producing more of their proteins. So we went on and
studied MNX1 more extensively," said Ittmann.
The scientists discovered that, compared with normal prostate
tissues, both African American and European American prostate cancer
have MNX1 genes that are more active and produce more of the MNX1
protein. However, MNX1 is significantly more active in African American
prostate cancer than in European American prostate cancer.
Further research shed light on what can increase MNX1 activity in prostate cancer and strengthened MNX1's ties to the disease.
"Interestingly, we found that both androgens, such as testosterone,
and AKT, a signaling pathway, increase MNX1 activity. It's been known
for quite some time that androgens and the AKT pathway play a central
role in prostate cancer," said Ittmann.
The scientists then determined whether increased MNX1 activity
affected a metabolic pathway prostate cancer uses to grow. Dr. Arun
Sreekumar, professor of molecular and cellular biology, who also is with
the Alkek Center for Molecular Discovery and the Verna and Marrs McLean
department of biochemistry and molecular biology at Baylor, performed
lipid analysis in African American prostate cancer tissues and showed
that products of lipid metabolism increased when compared with those of
normal prostate tissues.
"I am excited that these data highlight the existence of a
biological basis in health disparity in prostate cancer," said
In summary, in African American prostate cancer androgen and the AKT
signaling pathway can increase the activity of MNX1, which in turn
increases lipid metabolism. Increased lipid metabolism is a hallmark of
aggressive prostate cancer, which is more common on African American
These results can potentially lead to new approaches to treat and
diagnose prostate cancer. For instance, currently, there are medications
available to control lipid synthesis, which allows for exploring the
effect of targeting lipid synthesis on prostate cancer growth. The
scientists will also explore whether MNX1 can help predict cases of
aggressive prostate cancer in the clinic.
"The better we can understand different subsets of prostate cancer,
for instance, prostate cancer from African American men, the better we
can treat them. A "one-size-fits-all" approach to treatment may not work
for all patients," said Creighton.