University of Pennsylvania scientists have uncovered variations around two genes that are associated with an increased risk of testicular cancer. The discovery, appearing in 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 factors that can account for most cases of testicular cancer," says Katherine L. Nathanson, a specialist in medical genetics. "These variants are the first striking genetic risk factors found for this disease to date."
Nathanson 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.
Testicular cancer is the most common cancer among young men, and its incidence has doubled in the last 40 years. 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 explained. "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 you carry two copies of the less common variant you are probably at incredibly low risk." She added that the magnitude of the risk associated with the KITLG is much larger than has been found in similar studies of other adult cancers, such as prostate cancer. In other cancers, individual genes increase a person's risk by 10 to 25 percent, whereas the KITLG gene is associated with a whopping 300 percent increase in risk for testicular cancer.
By using the newly-discovered genetic risk factors as a lens, the researchers believe they may now be able to reveal critical environmental factors that trigger the cancer. "We are very interested in how genes and environmental factors work together to increase one's risk," Nathanson says. "Now that we know something about the genetics, we hope to now build a better model of who is at risk by looking at gene-environment interactions."
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Source: University of Pennsylvania School of Medicine
