Testicular Cancer Risk Among Caucasians a Trade-Off for Skin Protection

Increased testicular cancer risk among Caucasian men is a result of a trade-off to protect them from harmful ultraviolet rays.

Scientists said the increased risk Caucasian men have of testicular cancer in comparison to African men is a result of their lighter skin.

Study author Douglas Bell, from the National Institute of Environmental Health Sciences at the National Institutes of Health, said they have identified a DNA sequence variation in a protein implicated in cancer that is more prevalent in Caucasians than Africans.

He said the p53 variation is associated with a very large risk of testicular cancer, but potentially protects light-skinned men from UV rays.

Half of human cancers are associated with mutations in the p53 gene. It must activate a wide range of genes to influence cancer-related signalling pathways.

Bell and Gareth Bond, from the University of Oxford and the Ludwig Institute for Cancer Research, suggested cancer risk could be associated with genetic variations in p53 binding sites.

Mortal threat to ancestors

Published in the journal Cell, Bell said: "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."

During their study, they found one of the variants affecting a p53 binding site was located in the KITLG gene, which is linked to testicular cancer.

They found that KITLG activation by p53 is crucial for cancer processes, including cell proliferation, and found it was much more common in Caucasians than Africans, explaining why testicular cancer is more common among the latter.

Bell and Bond believe this variant may be selected in lighter-skinned men during evolution because the KITLG gene plays an important role in triggering the protective tanning response to UV rays.

Bond said: "It seems that over the long course of human evolution, the trade-off might have worked well enough to boost the frequency of the [variant], especially in the European Caucasian population.

"I'd speculate that serious sun damage to skin would have posed a mortal threat to our early ancestors."