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Quarter of sun-exposed skin samples had DNA mutations

Friday 22 May 2015

A sobering BBC News headline greets sun worshippers on the eve of the spring bank holiday: "More than a quarter of a middle-aged person's skin may have already made the first steps towards cancer."

Sunlight is made up of ultraviolet (UV) radiation. Low levels of exposure to UV light are actually beneficial to health – sunlight helps our bodies produce vitamin D.

But prolonged exposure can change (mutate) the DNA in the cells. Over time the mutations accumulate, turning the skin cells cancerous, which can lead to either non-melanoma or melanoma skin cancer.

As part of a study into skin cancer, researchers analysed skin removed from the eyelids of four people aged 55 to 73 known to have a varying history of sun exposure (but not a history of cancer) to see what DNA mutations had built up.

To their surprise they found hundreds of normal cells showing DNA mutations linked to cancer, called "mutant clones", in every 1sq cm (0.1 sq in) of skin, and there were thousands of DNA mutations per cell.

The results were based on skin cells from the eyelids of just four people, so we don't yet know if the same would be found in other skin areas, or in other people, or what proportion of the mutated cells would eventually progress to skin cancer. 

Where did the story come from?

The study was carried out by researchers from The Wellcome Trust Sanger Institute in the UK, and was funded by The Wellcome Trust and the Medical Research Council.

It was published in the peer-reviewed journal, Science.

The BBC and the Daily Mail reported the story accurately and reiterated the best ways to lower your risk of getting skin cancer. 

What kind of research was this?

This was a genetics study looking at changes in the DNA of normal skin cells to see what proportions were linked to cancer.

Skin cancer is one of the most common forms of cancer. There are two main types of skin cancer:

  • non-melanoma skin cancer – where cancer slowly develops in the upper layers of the skin; there are more than 100,000 new cases of non-melanoma skin cancer every year in the UK
  • melanoma skin cancer – a more serious type of skin cancer; there are around 13,000 new cases of melanoma diagnosed each year in the UK and 2,000 deaths

Radiation from too much sun exposure causes damage to the DNA of skin cells. When certain combinations of mutations accumulate, the cell can become cancerous, multiplying and growing uncontrollably. 

Scientists know about lots of skin cancer mutations, but these tend to have been studied using samples of cancerous skin cells. Researchers don't know what combination of mutations is needed to transform healthy skin cells into cancer, or in what order.

Approaching the problem from a different direction, this team looked at healthy skin cells to see what mutations might be accumulating in a pre-cancerous stage. 

What did the research involve?

The scientists analysed the DNA of healthy eyelid skins cells removed from four people during plastic surgery (blepharoplasty). They looked for DNA mutations they knew were linked to cancer later on. The removed eyelid skin was reported to be normal and free of any obvious damage.

The team used eyelid skin because of its relatively high levels of sun exposure and because it is one of the few body sites to have normal skin removed.

They say this procedure is performed for age-related loss of elasticity of the underlying skin, which can cause eyelid drooping sometimes severe enough to disrupt vision, although the epidermis remains otherwise normal.

The skin sample donors were three women and one man, aged 55 to 73. Two had low sun exposure, one moderate and one high. Three were of western European origin and one was of south Asian origin. It was not clear how sun exposure was assessed.  

What were the basic results?

The researchers found a lot more cancer-related mutations in the normal cells than they were expecting. In all, their analysis pinpointed 3,760 mutations. The pattern of DNA mutations "closely matched" those expected for UV light exposure and that seen in skin cancers. 

DNA is made up of a code of letters known as base pairs. The team estimated people have around two to six mutations per million base pairs per skin cell. This, they said, was lower than the number of mutations usually found in skin cancer, but higher than found in other solid tumours.

Overall, they estimated around 25% of all skin cells carried a certain type of cancer-linked mutation called NOTCH mutations. While not enough to cause cancer on their own, if other mutations accumulate on top of the NOTCH mutations, they may cause cancer in the future. 

How did the researchers interpret the results?

Dr Peter Campbell, head of cancer genetics at Sanger, told the BBC News website: "The most surprising thing is just the scale; that a quarter to a third of cells had these cancerous mutations is way higher than we'd expect, but these cells are functioning normally."

He added: "It certainly changes my sun worshipping, but I don't think we should be terrified … It drives home the message that these mutations accumulate throughout life, and the best prevention is a lifetime of attention to the damage from sun exposure." 


This study estimated around 25% of normal skin cells have DNA mutations that could prime them to develop into skin cancer in the future. This was a lot higher than the scientists expected.

The genetic analysis of the study was robust, but used skin samples from just four people. This severely limits the generalisablity of the findings to the general population. For example, the results might be different for people of different ages, sun exposures and skin colours, so we don't know if this is true for most people.

Similarly, the researchers only used eyelid cells. There may be something unique about eyelid tissue that is linked to this higher than expected mutation rate. This may or may not be true for skin from other areas. At the moment, we don't know if the one in four estimate applies to other skin areas.

The good news is there are simple and effective ways of reducing your risk of skin cancer. The best way to prevent all types of skin cancer is to avoid overexposure to the sun and to keep an eye out for new or changing moles.

A few minutes in the sun can help maintain healthy levels of vitamin D, which is essential for healthy bones, but it's important to avoid getting sunburn. Wearing protective clothing such as sun hats, seeking shade, and wearing sun cream of at least SPF 30 are all advised.

Read more about how to enjoy the benefits of the sun without exposing your skin to damage

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Quarter of skin cells 'on road to cancer'

BBC News, 22 May 2015

Skin cancer alert for the over-50s: Millions failing to heed advice over sun damage

Daily Mail, 22 May 2015

Links to the science

Martincorena I, Roshan A, Gerstung M, et al.

High burden and pervasive positive selection of somatic mutations in normal human skin

Science. Published online May 22 2015