HOXB13: Indeed a Major Susceptibility Gene for
Some people are born with the tendency to develop cancer. For example, a woman’s risk for breast cancer is greatly increased when she inherits a damaged copy of the genes, BRCA1 or BRCA2. And now we know, thanks to the work of William Isaacs, Ph.D., and colleagues, that when a man inherits a mutated form of a gene called HOXB13 (which is important in normal prostate development), his chances of developing prostate cancer are greatly increased.
Doctors and scientists have known for many years that prostate cancer runs in some families, and that for men in these families, prostate cancer seems to develop sooner than it does in other men. But "uncovering the molecular basis for an inherited form of this disease has been challenging," says Isaacs, the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology. Last year, in a genetic study of families with prostate cancer, Isaacs and colleagues at the University of Michigan identified a rare mutation of HOXB13, called G84E, is present in men with a family history of prostate cancer who develop the disease at a younger age. Since those findings were published, nine independent studies have confirmed that HOXB13 is a prostate cancer susceptibility gene. Studies from the International Consortium for Prostate Cancer Genetics, the largest collection of hereditary prostate cancer families in the world, and separate analyses of individual study populations, all have reported that men who inherit the G84E form of the gene have a higher likelihood of developing prostate cancer, with increases in risk ranging from four- to 16-fold.