A new study including more than 25,000 men has uncovered four new genetic variants associated with increased risk of testicular cancer. Testing for these variants, combined with all 21 previously identified variants using genetic sequencing, identified men with a 10-fold higher risk of testicular cancer than the population average. This research was published in Nature Communications (2015; doi:10.1038/ncomms9690).

The research, led by scientists at The Institute of Cancer Research (ICR) in London, England, is the largest study to date of the genetics of testicular germ cell tumors, which is the most common cancer in young men. Funding for the study was provided by the Movember Foundation, ICR, and Cancer Research UK.

Researchers discovered the four new variants through analyzing the DNA of 6059 patients with testicular cancer, and compared with the DNA of 19 094 people who did not have the disease.

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The sizes of the effects of some of the genetic variants associated with testicular cancer risk are quite high when compared with breast and prostate cancer, for example, where most variants each have only a very small effect. A man in the top 1% of genetic risk had a 5% lifetime risk of developing testicular cancer, more than 10 times higher than that of the average man.

There are no current treatment options that target specific genetic mutations in testicular cancer, and standard treatment with platinum-based chemotherapy has a high success rate. Indicating that the more likely application of genetic testing in testicular cancer is in diagnosing the level of risk for men yet to develop the disease, rather than in matching patients to specific treatments.

However, understanding the genetic variants underlying susceptibility to testicular cancer also helps us understand the biology of the disease, which may in due course inform development of new targeted therapies that could be effective in patients resistant to platinum chemotherapy.

Carrying two copies of a single-letter change in the DNA of chromosome 16 led to a 35% increase in activity of the GSPT1 gene in men with testicular cancer compared with those who do not have testicular cancer. This gene has a role in controlling cell division and is proven to have increased activity in cancers of the breast, stomach, and prostate.

“Our study identified four new genetic risk factors for testicular cancer. Through previous studies, many led by our team at the ICR, this brings the total number of genetic variants known to be associated with testicular cancer to 25,” said Clare Turnbull, MRCP, PhD, senior researcher at ICR and honorary consultant at The Royal Marsden.

“Applying these 25 variants, we found that men in the top 1% for testicular cancer risk were at a more than 10-fold elevated risk of developing the disease compared with the average—although that still adds up to only around a 5% (1 in 20) chance of developing testicular cancer.

“In the future, if we can identify more of the genetic variation underlying testicular cancer, this sort of testing might be used clinically to help identify those at most risk of testicular cancer before they develop the disease, such that we can offer measures to help stop them from developing testicular cancer.”