Nearly half of testicular cancer risk comes from inherited genetic faults

The research suggests 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.

The findings suggest testing for a range of genetic variants linked to testicular cancer could be effective in picking out patients who are at substantially increased risk – potentially opening up ways of preventing the disease.

Scientists at The Institute of Cancer Research, London, along with colleagues in Germany, Sweden and the US, used two independent approaches to analyse the risk of testicular germ cell tumours – easily the most common type of testicular cancer. Their research is the largest study ever to explore testicular germ cell tumours in detail.

Researchers first 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 analysis revealed that 49% of all the possible factors contributing to testicular cancer risk are inherited.

It found that the inherited risk comes from a large number of minor variations in DNA code, rather than one faulty gene with a big 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.

Identifying more of these ‘hidden’ mutations could allow doctors to screen men for testicular cancer risk, increasing the chance of preventing the disease or catching it early.

Dr Clare Turnbull, Senior Researcher in Genetics and Epidemiology at the ICR, 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 behavioural 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. Institute of Cancer Research