31st May 2009

First testicular cancer risk genes found

Three DNA variants can increase risk fourfold

Location of testicular cancer risk genes.

Location of testicular cancer risk genes. The red lines mark the locations of the newly identified risk genes: SPRY4, on chromosome 5; BAK1, on chromosome 6; and KITLG, on chromosome 12.

Researchers have found the first inherited genetic risk factors for testicular cancer, according to research published online in Nature Genetics today.

A team led by scientists at The Institute of Cancer Research (ICR) compared the genes of 730 men who had developed testicular cancer with the genes of healthy men. They found many of the men who had suffered cancer shared common DNA variants on chromosomes 5, 6 and 12 that the healthy men did not have.

Their results mean that men who inherit any of these genetic variants are at a higher risk of developing the disease than those who do not. Inheriting the strongest of the three factors increases men's risk by two- to threefold, while inheriting all of them increases the risk by up to fourfold.

The publication of the research coincides with Everyman Male Cancer Awareness Month in June.

This study is an important step towards developing a targeted screening programme for relatives of men who have had testicular cancer.

"We have known for some time that men whose father, brothers or sons had testicular cancer are much more likely to get it themselves and we have been searching for this genetic link," one of the lead scientists, Dr Elizabeth Rapley from the ICR, says.

"In this research, we have identified three genetic factors linked to an increased risk of testicular cancer. We believe there are more still to be found and we are working on identifying the rest."

"The risk conferred by each gene differs, but in one case it is two-to threefold," Professor Mike Stratton from the Wellcome Trust Sanger Institute and the ICR says.

" It may be possible in future to identify men who are at high risk of developing testicular cancer, particularly those who have a brother or father already affected by the disease. This may allow early detection or prevention. "

Prof Mike Stratton

"The risks also add together to some extent, so that men who inherit all the risk variants we found are four times more likely than the general population to develop testicular cancer. By combining these genetic risks with other known risk factors it may be possible in future to identify men who are at high risk of developing testicular cancer, particularly those who have a brother or father already affected by the disease. This may allow early detection or prevention."

The study - funded by the Everyman Campaign, Cancer Research UK and the Wellcome Trust - has also given researchers a clue to the mechanism by which testicular cancer develops.

The three markers were all found near genes involved in the same biochemical pathway - one which is important in the survival and development of germ cells (cells that go on to form sperm). Disrupting this important pathway may be one mechanism by which cancer can grow.

"By understanding the biology of this disease we hope to improve treatment options," Dr Rapley says.

The researchers are now looking for up to 3000 men who have had testicular cancer to participate in the study to identify more genetic risk factors. These new volunteers would provide a blood sample and fill in a questionnaire.

"We are hopeful we can find more risk factors but we do need more people affected by testicular cancer to help in this research," Dr Rapley says.

"We are grateful to all those men who have participated in this study so far, and would like anybody who has suffered testicular cancer to contact us - even if they were treated 20 years ago. They could ultimately help us develop treatments and improve diagnostic techniques to improve the lives of sufferers in the future."

Notes to Editors

  1. Men interested in participating in the study can find more information at: http://www.everyman-campaign.org/testicular/research/TesticularCancerStudy.html
    Testicular cancer is the most common form of cancer in men aged between 15 and 44, with about 2000 cases a year in the UK. Incidence is increasing dramatically - almost fourfold in the last 50 years - but testicular cancer is 99 per cent curable if caught early, and with treatment the overall cure rate is 97 per cent. Studies have found the risk to brothers of testicular cancer patients to be eight to ten times higher than the general population; while for fathers of sufferers the risk is four to six times higher. These inheritance risk factors are much higher than for other cancer types, which are generally only twofold.
  2. Publication Details

    • A genome-wide association study of testicular germ cell tumor.

      Rapley EA, Turnbull C, Al Olama AA, Dermitzakis ET, Linger R, Huddart RA, Renwick A, Hughes D, Hines S, Seal S, Morrison J, Nsengimana J, Deloukas P, UK Testicular Cancer Collaboration, Rahman N, Bishop DT, Easton DF and Stratton MR

      Nature genetics 2009;41;7;807-10

    Participating Centers

    • Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK
    • Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK.
    • The Wellcome Trust Sanger Institute, Hinxton, UK
    • Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey, UK
    • UK Testicular Cancer Collaboration (See Nature Genetics for full details)
    • Section of Epidemiology & Biostatistics, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.

The Institute of Cancer Research

The Institute of Cancer Research is Europe's leading cancer research centre with expert scientists working on cutting edge research. In 2009, the ICR marks its centenary of world-leading research into cancer prevention, diagnosis and treatment. Scientists at the ICR have identified more cancer-related genes than any other organisation in world. These discoveries are allowing scientists to develop new cancer treatments. The ICR is a charity that relies on voluntary income. It is one of the world's most cost-effective major cancer research organisations with more than 95p in every £ directly supporting research.


The Everyman Male Cancer Campaign

Everyman is the UK's leading male cancer campaign which raises awareness of, and funds research into, testicular and prostate cancer. Everyman funds research at The Everyman Centre - Europe's first and only centre dedicated to male cancer research. Everyman is dedicated to improving the survival rate of men with testicular cancer by raising awareness about the early symptoms. Its scientists have also led groundbreaking research into new treatments for prostate cancer. The Everyman Centre is located within the ICR.


Cancer Research UK

  • Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.
  • Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer.
  • Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients.
  • Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make.
  • Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer.

For further information about Cancer Research UK's work or to find out how to support the charity visit:


The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.


The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.


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