Skin Cancer-related Mutations Higher in the UK Than Singapore
Northern European skin types in the UK have four times the burden of DNA mutations than the average skin type found in Singapore.
People in the UK have facial skin that is far more DNA damaged from the sun than people in Singapore, explaining the far higher risk of developing basal and squamous cell carcinomas in the UK, new research suggests.
When researchers from the Wellcome Sanger Institute and their collaborators at the Skin Research Institute of Singapore (SRIS) compared the mutational landscape of normal facial skin between individuals from the UK and Singapore, they found that Northern European skin types in the UK have four times the burden of DNA mutations than the average skin type found in Singapore.
The team found that most of the DNA mutations accumulated in Northern European skin types in the UK are due to UV light whereas in Singapore mutations are mainly due to usual ageing processes.
Singapore sits near the equator with a much higher typical UV level than the UK, but rates of keratinocyte cancers are 17 times higher in the UK, even though the cancer’s primary risk factor, UV light, is three times stronger in Singapore.
To arrive at their findings, researchers collected tissue samples from patients undergoing routine surgery to remove excess eyelid or eyebrow skin. The team sequenced the outermost layer of skin to identify genetic alterations, focusing on 74 genes commonly mutated in cancers. They analysed over 400 samples and compared tissue from five donors in Singapore with published sequencing data from six UK donors. Mean donor age from Singapore was 62 years old while UK mean age was 68.
Eyelid skin in the UK cohort had accumulated four times as many cancer-associated DNA mutations, particularly those affecting known ‘cancer genes’ such as TP53. Cells with these mutations out-compete other cells and are more likely to divide. 15% of UK skin cells had damage to the p53 protein, compared to just 5% of Singaporean skin cells. The scientists also detected an abnormal number of chromosomes in 13% of cells in UK skin, compared to just 1% of cells in Singapore. Scientists found that by 60 years of age, nearly every cell in the UK donor skin had a mutation in a cancer-associated gene.
The scientists next compared the germline genetics of the UK and Singaporean donors. Differences were found between the two populations in genes that produce pigmentation, which is known to protect cells against UV light, but also in genes related to inflammation, the immune system and some skin cancer genes. Together, these inherited differences affect the skin’s ability to protect itself from UV light as we age.
The ‘less protective’ Northern European skin type observed in the UK germline outweighs the fact that the UK has a far lower ground-level exposure to UV light than in Singapore. The researchers suggest inherited variations in skin-protective genes therefore play a vital role in shaping how our skin ages and responds to sunlight.
“These findings help us understand why the UK has such a high incidence of keratinocyte skin cancers,” says study author Dr Charlotte King, a postdoctoral scientist at the Wellcome Sanger Institute. “We hope our study encourages others to look at further diverse populations – across the spectrum of cancer risk – for clues on how we can better prevent this common cancer. “
Pigmentation in the skin can protect cells from UV rays, but other differences, like how the body copes with inflammation, may explain variation in cancer risk from person to person, King says. “Studying populations at a lower cancer risk can teach us about protective mechanisms that already exist in nature.”
Dr Phil Jones is senior author of the study, senior group leader at the Wellcome Sanger Institute, professor of cancer development at the University of Cambridge and consultant at Addenbrooke’s Hospital in Cambridge. “Our study shows that people in the UK lack the genes that protect our skin against the sun,” he says. “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.”
The findings are published in Nature Genetics.
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