Testicular Cancer Risk Comes from Inherited Genetic Faults

Testing for a range of genetic variants linked to testicular cancer could be effective in picking out patients who are at substantially increased risk, and therefore, potentially opening up ways of preventing the disease.

Almost half of the risk of developing testicular cancer comes from the DNA passed down from parents and genetic inheritance is much more important in testicular cancer than in most other cancer types, where genetics typically accounts for less than 20% of risk.

Scientists at The Institute of Cancer Research (ICR; London, UK) along with colleagues in Germany, Sweden, and the USA, used two independent approaches to analyze the risk of testicular germ cell tumors which easily the most common type of testicular cancer. They used statistical analysis to examine patterns of ancestral testicular cancer in family groups across 15.7 million people from the Swedish Population Registry cancer family database, including 9,324 cases of testicular cancer. They then looked in detail at the genetic code of 6,000 UK men from two previous testicular cancer studies, 986 of whom had been diagnosed with the disease.

The combined Genome-Wide Complex Trait Analysis revealed that 49% of all the possible factors contributing to testicular cancer risk are inherited. They found that the inherited risk comes from a large number of minor variations in DNA code, rather than one faulty gene with a broad effect. Although substantial inroads have been made over the last five years at the ICR into identifying mutations associated with risk of testicular cancer, the study also showed that these known mutations only account for 9.1% of the risk of developing the disease. Therefore the majority of the genetic variants that raise testicular cancer risk have yet to be identified. There was a higher hereditability for seminomas at 42.2% as compared for non-seminomas at 29.4%.

Clare Turnbull, PhD, a senior author of the study, said, “Our study has shown that testicular cancer is a strongly heritable disease. Around half of a man's risk of developing testicular cancer comes from the genes he inherits from his parents, with environmental and behavioral factors contributing to the other half. Our findings have important implications in that they show that if we can discover these genetic causes, screening of men with a family history of testicular cancer could help to diagnose those at greatest risk, and help them to manage that risk.” The study was published on September 9, 2015, in the journal Scientific Reports.

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The Institute of Cancer Research