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Common Gene Variants Associated with Testicular Cancer

Testicular cancer is the most common cancer among young men between the ages of 15 and 40 and its incidence in non-Hispanic Caucasian men has doubled in the last 40 years. Researchers have now identified two common gene variants that are associated with increased susceptibility to this disease. This discovery lays the groundwork for genetic tests for susceptibility to testicular cancer which is over 90% curable if detected early. In a genome-wide association study, Dr. Katherine Nathanson, senior author of the report, and collaborators, 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 this gene. "This finding is quite different than those observed in many other genome-wide association studies," Dr. Nathanson said. "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.” “Our observed strong association is intriguing and may reflect the impact of the genetic effect of KITLG," lead author Dr. Peter Kanetsky noted. "However, since the prevalence of the common variant is so high, it may also reflect other underlying factors required in conjunction with KITLG for disease development. This remains to be determined.” Additionally, the new findings may begin to explain why white men are more often diagnosed with testicular cancer than African American men. KITLG is involved in pigmentation--and the version of this gene associated with testicular cancer is common in the white population, but much less common in the black population. This work was published on May 31 in the online edition of Nature Genetics. [Press release] [Nature Genetics abstract]