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Testicular cancer risk gene protects skin from sun damage

14 October 2013
Appeared in BioNews 726

A specific gene variant more common in caucasian men has been associated with an increased risk of testicular cancer, a study has found.

The authors go on to explain that the molecular mechanism involved may also protect skin cells from UV damage, suggesting that from an evolutionary perspective the mutation may have been positively selected in light skinned people.

Approximately half of all human cancers carry p53 gene mutations. The protein p53 is believed to be involved in processes that guard against cancer by causing cells to stop growing, sometimes even by killing them, in response to cell damage.

By looking at genome-wide data, researchers at Ludwig Cancer Research in Oxford, UK, and New York, USA, were able to identify a specific mutation – a single nucleotide polymorphism – affecting the operation of p53 that increased testicular cancer risk threefold.

'It appears that this particular variant permits testicular stem cells to grow in the presence of DNA damage, when they are supposed to stop growing, since such damage can lead to cancer', says Dr Douglas Bell, of the US National Institute of Environmental Health Sciences, who also worked on the study. 'The genetic risk factor we identified is associated with one of the largest risks ever reported for cancer', he added.

Using an evolutionary genomic analysis, the team then showed that other gene variants that affect the functioning of p53 have been negatively selected by evolution, slowly disappearing from our DNA.

However, the researchers then sought to explain why this particular gene variant had also resisted negative selection by indentifying that the same mechanism associated with increased cancer risk also protected light-skinned people from the harmful effects of UV light. The SNP causes cells to multiply, leading to a 'protective tan'.

'Over the course of evolution, as humans migrated out of Africa into the dimly lit terrain of the north, they developed lighter skin, most likely to adapt to the lower levels of sunlight', explains Dr Gareth Bond from the University of Oxford and co-author of the study. 'Unfortunately, that adaptation also left their skin susceptible to UV damage'.

Professor Tim Bishop, a Cancer Research UK expert in cancer genetics, said: 'This is a fascinating example of how ideas from evolutionary biology can be applied to large databases of human genetic information to discover the impact of particular DNA changes'.

'In the process, we learn more about the action of p53, a crucial cancer suppressing gene. It's too early to say how this could benefit cancer patients in the future but it's certainly an interesting addition to our understanding of cancer evolution'.

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