(PHILADELPHIA) Researchers at the University of Pennsylvania School of Medicine have uncovered variation around two genes that are associated with an increased risk of testicular cancer. Testicular cancer is the most common cancer among young men, and its incidence among non-Hispanic Caucasian men has doubled in the last 40 years -- it now affects seven out of 100,000 white men in the United States each year. The discovery, published in the May 31, 2009 online issue of Nature Genetics, is the first step toward understanding which men are at high risk of disease.
"Despite being quite heritable, there really have not been any clear genetic risk factor that can account for most cases of testicular cancer," says Katherine L. Nathanson, MD, an assistant professor of Medicine and a specialist in medical genetics at the Abramson Cancer Center. "These variants are the first striking genetic risk factors found for this disease to date."
Nathanson and co-author Peter A. Kanetsky, PhD, MPH, an assistant professor of Epidemiology, found that men who have two copies of the common version of the c-KIT ligand (KITLG) gene have a 4.5-fold higher risk of testicular cancer than men who have two copies of the less common or minor version of the gene. Additionally, men with two copies of the common version of variants next to another gene, sprouty 4 (SPRY4), have a 1.48-fold higher risk than men with two copies of the less common version of the gene.
While researchers suspect environmental exposures may play a part in the growing incidence, they now know that an individual's genes also play a major role in disease susceptibility.
"This finding is quite different than those observed in many other genome-wide association studies," Nathanson says. "In most studies, the increased risk of disease is associated with the less common variant of the gene. In this case, it is the more common variant in Caucasians that is associated with risk. If y
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University of Pennsylvania School of Medicine