NEW YORK — UK residents have a higher incidence of keratinocyte cancer than Singaporeans, who receive far greater sun exposure, because of inherent genetic differences and greater sun-related skin DNA damage, suggests a new study.
For a paper published in Nature Genetics on Wednesday, researchers from the Wellcome Sanger Institute and the Skin Research Institute of Singapore studied mutations in facial skin samples from UK residents and Singaporeans.
Their findings revealed mutational patterns in the skin samples from the UK that were convergent with cancer but were absent in the Singaporean samples.
Keratinocyte cancers are the commonest forms of human cancers, and the risk of developing them increases with repetitive exposure to ultraviolet (UV) radiation, mainly from outdoor work, sunbathing, and tanning beds. The authors wrote that Singapore, located near the equator, receives two to three times more UV radiation than the UK, yet keratinocyte cancer incidence is 17-fold lower in Singapore.
According to the study's lead author Charlotte King, a researcher at the Wellcome Sanger Institute, her team chose to study samples from Singapore and not any other equatorial country because it has a prominent skin research institute and keeps comprehensive medical records.
The researchers collected eyelid skin samples from five healthy donors in their 60s who underwent routine surgery to remove excess eyelid or eyebrow skin in Singapore. They used targeted sequencing to study the mutation patterns from over 400 donor samples and compared them with published sequencing data from six similar donors from the UK.
"Comparing healthy tissues from high- and low-risk populations can help us determine which mutations are involved in healthy cells turning cancerous," said King.
The findings indicated that the UK skin samples had four times more mutations than the Singapore samples. They especially noted mutation differences in SBS1 and SBS5 genes associated with tissue aging and SBS7 related to UV lesions and repair.
SBS1 and SBS5 mutations were higher in the UK than in Singaporean skin, indicating DNA damage caused by UV radiation.
The UK skin samples also had approximately ten times more copy number aberrations. Of note, mutations in TP53, a gene known to prevent cancer growth, were more prevalent in UK skin — 15 percent of UK skin cells had the TP53 mutation compared to just 5 percent of Singaporean skin cells.
Next, the researchers compared the germline genetics of the UK and Singaporean donors. They found mutation differences in genes that produce pigmentation, which is known to protect skin cells against UV rays. They also noted differences in genes related to inflammation and the immune system.
According to the authors, these inherent differences in genes responsible for UV protection play a vital role in shaping how the skin ages and responds to sunlight, determining the risks of developing skin cancers. The "less protective" Northern European skin type observed in the UK germline outweighs that the UK has a far lower ground-level exposure to UV light than Singapore, the researchers noted in a statement.
To ensure their findings weren't a result of bias in sequencing cancers in white Europeans, they analyzed keratinocyte cancer data from South Korea. Their findings suggested that normal UK skin has multiple features convergent with cancer, whereas normal Singaporean skin does not.
Philip Jones, senior author of the study, said that the findings show that people in the UK must exercise sun-safe behaviors, such as wearing protective clothing, using sunscreen, and seeking shade during peak UV hours.