The statistics have been clear for a long while now: African American men are more susceptible to prostate cancer. In fact, they have about one-and-a-half times the incidence and twice the mortality associated with prostate cancer of European Americans.
Why is that?
Scientists, having sifted through the widely diverse prostate genetics records maintained by Baylor University, think they may at last have isolated the gene, and discovered the culprit.
"We found 24 genes that were different between the African American and the European American prostate cancer datasets," said Dr. Michael Ittmann, professor of pathology & immunology at Baylor and the Michael E. DeBakey Department of VA Medical Center. "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."
As far as genes go, MNX1 is one of the bad boys. It has been associated with Currarino syndrome, a congenital spinal disorder, and linked to infantile acute myeloid leukemia, a rare cancer of the bone marrow and lymph nodes.
"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.
European American men's prostate cancer has MNX1 activity that produces the problem proteins as well, but MNX1 is significantly more active in African American prostate cancer than in European American prostate cancer. So having discovered who the bad actor may be, scientists are now turning heir attention to the source of the increased MNX1 activity in prostate cancer patients.
"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.
And everything is connected: increased lipid metabolism has long been known as a hallmark of aggressive prostate cancer, which is more common on African American men. Scientists from Baylor dug deeper, and discovered that increased MNX1 activity accelerated lipid metabolism.
The upside to all this – besides th better understanding it gives us regarding African American men's susceptibility to prostate cancer – is that the results can potentially lead to new approaches to treat and diagnose the disease. Existing medications used to control lipid synthesis may be re-purposed as prostate cancer inhibitors, or we may be able to predict cases of aggressive prostate cancer through monitoring of MNX1 activity.
The research was published in the journal Cancer Research.