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Genetic reason why light-skinned people in UK are at higher risk of certain skin cancers explained by Wellcome Sanger Institute





Light-skinned people in the UK lack the genes that protect against the damage caused by ultraviolet (UV) radiation, putting them at higher risk of developing the most common skin cancers, scientists at the Wellcome Sanger Institute have found.

The researchers found those with northern European skin types have DNA damage as a result of being exposed to UV light from sunlight, tanning beds, or both.

Light-skinned people in the UK lack the genes that protect against the damage caused by ultraviolet (UV) radiation, a study has shown
Light-skinned people in the UK lack the genes that protect against the damage caused by ultraviolet (UV) radiation, a study has shown

The team compared skin tissue samples, taken from the eyelid, from people in the UK and Singapore.

The findings, published in the journal Nature Genetics, showed DNA mutations in northern European skin types in the UK were due to UV radiation, whereas in Singapore, the changes were largely due to usual ageing processes.

The researchers said the “less protective” northern European skin type puts light-skinned people at far higher risk of developing keratinocyte or non-melanoma cancers.

Dr Charlotte King, first author of the study and postdoctoral scientist at the Sanger Institute in Hinxton, said: “These findings help us understand why the UK has such a high incidence of keratinocyte skin cancers.

“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.”

Singapore sits near the equator and the UV level there is three times stronger than the UK.

But keratinocyte cancer rates are 17 times higher in the UK, with about 156,000 cases a year, compared with Singapore.

Analysis of more than 400 samples showed the UK cohort had four times as many cancer-associated DNA mutations, particularly those affecting known cancer genes such as TP53.

The team also found abnormal number of chromosomes – long DNA molecules – in 13% of cells in UK skin, compared with just 1% of cells in Singapore.

The researchers said that by 60 years of age, nearly every cell in the UK donor skin had a mutation in a cancer-associated gene.

The scientists then compared the germline genetics – inherited DNA from parents – of the UK and Singaporean donors.

The team found that even though Singapore has a far higher ground-level exposure to UV light than the UK, people there had inherited gene variations that had a protective effect on their skin.

These included genes relating to pigmentation, which is known to protect cells against UV light, as well as genes associated with inflammation and the immune system.

Dr King said: “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.

“Studying populations at a lower cancer risk can teach us about protective mechanisms that already exist in nature.”

Dr Phil Jones, 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, added: “Our study shows that people in the UK lack the genes that protect our skin against the sun.

“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.”



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