'Secret ginger gene' may increase skin cancer risk for millions

“People can carry a ‘silent’ red hair gene that raises their risk of sun-related skin cancer, experts warn,” BBC News reports.

Research suggests that carrying just one copy of a variant of the MC1R gene (having two copies causes red hair) increases skin cancer risk, even for people without red hair.

The variant is called an R allele, people who have two R allele variants tend to have ginger hair, pale skin, freckles and burn easily in the sun. These people are known to be at higher risk of skin cancer; both non-melanoma and melanoma.

However, many people have one R allele variant (some reports claim 25% of the UK population are carriers), which doesn’t necessarily produce red hair. Researchers wanted to look at the DNA of skin cancers to see whether there was a difference at a genetic level between cells from people with R alleles and those without.

They found more genetic mutations in tumours from people with one or two R allele variants.

They report little difference between mutation levels with one R allele or two R alleles – meaning that people with one R allele who don’t have ginger hair could be at the same raised risk of skin cancer.

The study reinforces that point that people of all hair types and skin colour are at risk of skin cancer; not just pale white people with red hair. People often forget that reggae legend Bob Marley died of skin cancer aged just 36. 

Where did the story come from?

The study was carried out by researchers from the Wellcome Trust Sanger Institute, Universidad Nacional Autonoma de Mexico, Boston University School of Medicine, Cambridge Biomedical Campus, Royal College of Surgeons in Ireland, Yale University School of Medicine and the University of Leeds and was funded by Cancer Research UK and the Wellcome Trust.

The study was published in the peer-reviewed journal Nature Communications, on an open-access basis, meaning it is free to read online.

Most of the UK media focused on the increased risk of skin cancer for people with the “hidden ginger” gene, although there was a tendency to overstate the reliability of the findings.

The Daily Mail says that “Carrying the ‘ginger gene’ is as dangerous as 21 years of sun exposure as it raises the risk of deadly skin cancer.” But the researchers say that other factors, such as the likelihood of people trying to avoid sunburn (people with darker hair and /or complexion may spend more time in the sun), may have confounded their results.

The Guardian and BBC News provided the best overviews of the study and included useful discussions of the implications of the results.

What kind of research was this?

This is a cohort study, which examined cells from tumours removed from 405 people diagnosed with melanoma skin cancer (the more dangerous type). Researchers wanted to know whether the R allele gene variant influenced the numbers of mutations in cell DNA from these cancers. They hope this will help them understand the way these cancers develop.

Cohort studies can show links between factors, but they cannot show whether one factor (in this case, presence of the MC1R R allele) causes another (the number of DNA mutations found in cells).

What did the research involve?

Researchers analysed the DNA of tumour samples from 405 people diagnosed with melanoma skin cancer. They checked whether the samples had one or two R allele gene variants, then measured the numbers of DNA mutations from the six main classes of mutation.

The numbers of mutations were compared within the six classes, and overall, and they calculated the size of the difference in terms of how many years of sun exposure they could represent.

Researchers used samples taken from two separate patient groups. For all patients, they were able to adjust figures to take account of people’s age, sex and where the sample was taken from (the initial tumour or a secondary tumour). For 132 people (one of the groups) they could also take account of factors including which centre the patient had been treated at and clinical characteristics of the tumour.

In addition to the primary research question, the researchers also did some laboratory tests on cell lines, to see whether the R allele variants affected cell activity associated with DNA repair.

What were the basic results?

Tumours from people with one or two R allele variants had a 42% higher level of DNA mutations, compared to people without R allele variants (95% confidence interval 15% to 76%).

Importantly, there was little difference in the levels of mutation seen among people with one R allele compared to two R alleles. This might mean that people without the tell-tale ginger hair and freckles associated with two R alleles are at the same skin cancer risk, but without knowing it.

Cell cultures in the laboratory showed reduced DNA repair activity in cells with R allele variants.

How did the researchers interpret the results?

Researchers said the increase in one type of DNA mutation found among R allele variant carriers was comparable to what you might see after an additional 21 years of ageing.

They said the finding that one or two R alleles had similar effects on DNA mutations “suggests that the majority of persons with one R allele, who do not have a red hair/sun sensitivity phenotype, may still be highly susceptible to the mutagenic effects of UV light.” In other words, even if they don’t have red hair or burn easily, sunlight may still influence their DNA to mutate.

However, they warned there are other factors to consider: “It has been suggested that red haired, sun-sensitive individuals are more likely to practice sun avoidance, a factor that confounds ready interpretation of the association between mutation count and number of R alleles”.

So if people with red hair are more likely to avoid the sun, people without red hair but with an R allele variant may pick up more DNA mutations because they are exposed to more sun.

Conclusion

The study adds more weight to the importance of using sun protection to avoid skin cancer. We already know that people with red hair and freckles who burn easily are at increased risk of skin cancer.

This study suggests other people may also have a higher risk, without knowing it. Taking sensible sun protection measures makes good sense for everyone.

The findings are also useful for researchers, as they add to our understanding about how certain genetic traits affect the development of skin cancer. If DNA repair is reduced in people with some gene variants, sun damage may not be the only thing affecting their chances of getting skin cancer.

The study has limitations due to the type of research. It cannot tell us that these gene variants directly cause skin cancer, although it seems likely they are involved in some way. It’s important to remember that not everyone in the study carried these gene variants – around half did not have R alleles, but they did have skin cancer. So while R alleles may raise the risk of skin cancer, the lack of an R allele gene variant does not mean you won’t get it.

It’s worth noting that the confidence interval for the increase in DNA mutations is quite wide, making it difficult to be precise about the increased level of mutation. This means the reported “21 years of ageing” comparison might not be accurate.

Whatever your hair colour, eye colour and skin colour, the advice on protecting your skin from the harmful effects of the sun remains the same.

Links To The Headlines

Hidden red hair gene a skin cancer risk. BBC News, July 12 2016

Scientists closer to understanding why red hair genes increase skin cancer risk. The Guardian, July 12 2016

Beware the silent ginger gene: Even brunettes and blondes can carry ‘red-head gene’ which is as dangerous to skin as 21 YEARS of sun exposure. Daily Mail, July 13 2016

Millions of ‘secret gingers’ carry the gene which raises risk of skin cancer. The Daily Telegraph, July 13 2016

People with a ‘hidden’ ginger hair gene are officially more at risk of getting skin cancer. The Sun, July 12 2016

Hidden ginger gene puts 25% at greater risk of skin cancer. The Times, July 13 2016 (subscription required)

Links To Science

Daniela Robles-Espinoz C, Roberts NH, Chen S, et al. Germline MC1R status influences somatic mutation burden in melanoma. Nature Communications. Published online July 12 2016