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Genetic Susceptibility to Prostate Cancer: Are African Americans More Vulnerable?

Prostate cancer hits some groups of men much harder than others. It's much more common in African Americans, for instance, than in Asian men. Could it be that black men in this country are somehow more susceptible genetically than white or Asian men?

Scientific evidence suggests that the development of cancer is like a toppling row of dominos, in that a whole chain of genetic events must occur before a tumor can begin to grow. Inherited mutations in one or more genes (as believed to be the case in hereditary prostate cancer -- click here for more) probably speed up the body's journey toward cancer; presumably, in some men, a few of these dominos are already downed at birth. Environmental variables such as diet -- what men eat and drink (see prevention story by clicking here) and how they live -- may knock over the rest.

Somewhere in between these two is genetic susceptibility: Not exactly a mutation that causes cancer, but a genetic makeup that creates a more hospitable atmosphere -- which makes it easier for cancer to set foot in the door. In the domino analogy, perhaps genetic susceptibility tilts the table slightly, making the dominos more likely to fall, without actually knocking them over.

Evelyn R. Barrack, Ph.D., believes a slight variation she's found in the androgen receptors of men with prostate cancer -- the main switch plate through which the prostate is controlled by hormones -- may make men more susceptible to developing prostate cancer, and particularly to developing more aggressive disease. This variation, a "short repeat" in a sequence of proteins, is more common in African American men -- and may help explain why these men are at higher risk of developing prostate cancer. It's also more common in Caucasian men with clinically localized prostate cancer (cancer that appears to be curable) who are found after surgery to have micromestases -- tiny bits of cancer that have escaped the prostate and taken root elsewhere.

This short repeat may make testosterone more efficient in prostate cells, so that the same amount of testosterone goes further, and has more of an effect than in other man. It may be that men with longer repeats have better cancer-suppressing "brakes," -- better checkpoints for controlling cell division -- and men with the short repeat are more susceptible to developing prostate cancer -- and to developing a particularly nasty, more aggressive form of the disease.

Further Reading
"Androgen Receptor Gene Structure and Function in Prostate Cancer," World Journal of Urology, Vol. 14, pp. 329-337, 1996. Jeanette M. Hakimi, Rachel H. Rondinelli, Mark P. Schoenberg, Evelyn R. Barrack.


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