Researchers have discovered variation around two genes that are associated with an increased risk of testicular cancer. This discovery is the first step toward understanding which men are at high risk of testicular cancer, which now affects seven out of 100,000 white men in the United States each year. 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.

"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, study author. "These variants are the first striking genetic risk factors found for this disease to date."

Nathanson and co-author Peter A. Kanetsky 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 of testicular cancer 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 of testicular cancer, 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 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," Kanetsky says. "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."

Only a small proportion of men who carry the high-risk alleles will develop testicular cancer. The key now, the researchers say, is to find out what modifies the genetic risks and pushes one individual toward cancer while another remains disease-free. 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 would otherwise be lost in cloud of confounding information.

"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."

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.

Finally, Nathanson says the findings show that previous models of testicular cancer formation are correct and underscore why men with testicular cancer may also have fertility problems. "Researchers have postulated testicular cancer was a disorder of germ cell development or maturation, and they were right," she says. "The KITLG gene is critical for germ cell development and maturation."

Related Articles


Olive Oil Might Contribute to a Lowering of Breast Cancer Risk New research published in the journal BMC Cancer sheds more light on the suspected association between olive oil-rich Mediterranean diets and reductions in breast

New Technique Could Enable Earlier Detection of Melanoma Scientists are reporting development of a substance to enhance the visibility of skin cancer cells during scans with an advanced medical imaging system that combines

Researchers Develop 3 Minute Test for Prostate Cancer According to researchers, a new 3-minute test could help in diagnosing prostate cancer. Prostate cancer is one of the most common types of cancer in men, affecting

Coffee Consumption Inversely Associated With Risk of Prostate Cancer Research has revealed a strong inverse association between coffee consumption and the risk of lethal and advanced prostate cancers. "Coffee has effects on insulin

Reishi Mushroom and Green Tea for Cancer Prevention Both the reishi mushroom (Ganoderma lucidum; Lingzhi) and green tea have long held a place in traditional medicine in China and other Asian countries, for the general

References:
1. Katherine L. Nathanson, et al. University of Pennsylvania School of Medicine.

Add comment

User Name (Required)

E-mail (Required - Never shown publicly)

Website (Optional)

Notify me of follow-up comments

If you cannot read the code click to refresh for a new code.

Add comment

Cancel