UV protection gene variants lacking in white people

White people living in the UK are at a higher risk of developing the most prevalent type of skin cancer, due to the absence of protective genetic variants that shield them from UV damage.

Researchers from the Wellcome Sanger Institute in Cambridgeshire and the Skin Research Institute of Singapore compared tissue samples from people with Northern European skin types and Singaporeans. The results, published in Nature Genetics, showed that DNA mutations found in the samples from Northern European skin were mainly caused by UV radiation, while mutations in the Singaporean samples were chiefly due to the normal ageing process.

'Our study shows that people in the UK lack the genes that protect our skin against the sun' said senior author Dr Phil Jones, from the Sanger Institute. His colleague, first author Dr Charlotte King added: 'These findings help us understand why the UK has such a high incidence of keratinocyte skin cancers.'

Singapore lies close to the equator and UV levels are three times higher than in the UK, but keratinocyte cancer rates are 17 times higher in the UK, where it affects about 156,000 people every year. Keratinocyte cancer is the most common type of skin cancer worldwide and includes basal and squamous cell carcinomas, but not the rarer melanoma. It is closely linked to a person's lifetime exposure to UV radiation through either the sun or tanning beds.

The researchers collected over 400 samples from patients that underwent routine surgery to remove excess eyebrow or eyelid skin and compared the mutational landscape of the outermost layer of skin, focusing on 74 genes that are commonly mutated in cancer.

They found that people from the UK had four times as many cancer-associated mutations in their skin cells, with for example the well-known cancer-associated gene TP53 being damaged in 15 percent of the UK cohort skin compared to only five percent in the Singaporean skin cells. People from the UK cohort also harboured abnormal chromosomes in 13 percent of their cells compared to people from Singapore, who showed abnormal chromosome numbers in only one percent of their cells. The researchers reported that, by the age of 60, nearly every cell from the UK donor skin had a mutation in a cancer-associated gene.

The findings demonstrate the importance of understanding the difference in the genetic basis of  cancer susceptibility between certain populations and could help pave the way for more personalised approaches to cancer prevention.

Dr Jones said: 'Making sure we remember sun-safe behaviours, such as wearing protective clothing, using sunscreen, and seeking shade during peak UV hours is incredibly important for all, but as this study shows, especially for some genetically high-risk populations.'