‘Evolutionary trade-off’ links testicular cancer to tanning response

A DNA variation linked to testicular cancer may have emerged because it also helps protect light-skinned people from sun damage.

Despite the increase in testicular cancer risk associated with the DNA variation, the US and UK study concludes that it may have been favoured by natural selection to become more common in light-skinned people because of its ability to protect against sun damage.

The study, published in Cell, looked at small genetic variations known as single-nucleotide polymorphisms (SNPs) that account for many of the differences between people, from the colour of their hair to their risk of developing diseases like cancer.

Specifically, they looked at SNPs linked to a major cancer-associated molecule called p53.

Dr Douglas Bell of the US National Institute of Environmental Health Sciences and Dr Gareth Bond of Oxford University found a single SNP that was strongly linked to an increased risk of testicular cancer in Caucasian men.

Around half of cancers have been linked with faults in p53, which switches on genes linked to important cancer-related processes. The researchers reasoned that SNPs located at the point in DNA where p53 attaches itself, might disrupt how effectively it does its job and could be linked to cancer.

These attachment sites are known as ‘response elements’ and of the 62,567 SNPs that have been linked with cancer, the researchers found only a single SNP fell within a p53 response element.

The SNP boosts the strength with which p53 binds to the DNA and is associated with increased risk of testicular cancer. It increases production of a protein called KIT ligand (KITLG), which can power the multiplication of cells.

Bell explained: “The genetic risk factor we identified is associated with one of the largest risks ever reported for cancer.”

“We think it might prove useful for identifying individuals at the highest risk for cancer or who might benefit from preventive or therapeutic treatments.”

SNPs located in important DNA regions are rare and can be lost during evolution due to their occasional disease-promoting effects.

In this case, the SNP was found to be much more common in the European Caucasian population than in the African population.

The researchers suggest that this SNP may have become established within the Caucasian population due to a link between the KITLG gene and the tanning response required to protect lighter skin from UV damage.

“It seems that over the long course of human evolution, the trade-off might have worked well enough to boost the frequency of the SNP, especially in the European Caucasian population,” Bond says.

He speculates that the variation in the KITLG response element might be “evolution’s compensation”, becoming more prevalent in those that needed to protect their skin from UV damage.

“But it appears to come at a cost – which is greater risk for testicular cancer.”

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.”

Copyright Press Association 2013