The Times says “the anti-cancer gene fails in the sunshine”, among many reports on why people with red hair may be more susceptible to malignant melanoma – the most severe form of skin cancer.
The findings come from mainly laboratory-based research focused upon a protein called MC1R. Certain variants of this protein are known to be associated with red (or "ginger") hair colour, fair skin and vulnerability to being sunburned. People with these gene variants are also more likely to get melanoma, although the biology behind this is poorly understood.
The researchers found that the “normal” form of MC1R protects a cancer-suppressing protein called PTEN from being broken down when skin cells are exposed to ultraviolet light (UV) light. UV light – a form of radiation emitted by the sun, as well as artificial sources such as tanning lamps – is the leading cause of skin cancer.
But the “ginger” version of MC1R (RHC variants) does not. So exposure to UV light can break down PTEN leading to an increased risk of melanoma.
This research furthers the understanding of the biological mechanisms by which malignant melanoma may develop – though these mechanisms are likely to be complex, and this study alone only provides a piece of the puzzle.
Where did the story come from?
The study was carried out by researchers from Boston University School of Medicine, Harvard Medical School, and various other academic institutions worldwide. The study received various sources of financial support including the US National Institutes of Health and the American Cancer Society.
The study was published in the peer-reviewed scientific journal Molecular Cell.
The media coverage is generally representative of the findings of this study. The Mail Online’s headline “Redheads are '100 times more susceptible to the most lethal form of skin cancer'” may suggest that this is a new finding. However, this link was already known, and the current research has looked into why this link might exist.
What kind of research was this?
This was laboratory research that aimed to explore the possible biochemical mechanisms that make people with red hair more susceptible to melanoma, the most serious form of skin cancer. As well as red hair, various factors are known to increase risk of melanoma, including increased UV exposure, fair skin, having a greater number of moles, and family history of skin cancer.
Earlier research has indicated that certain variations in the gene encoding a protein found in skin pigment cells called the melanocortin-1 receptor (MC1R) lead to red hair, fair skin and poor tanning ability. People carrying these variations, called “RHC variants”, are also more susceptible to melanomas.
MC1R is activated by a hormone that stimulates pigment cells upon exposure to UVB light. In the current study the researchers wanted to assess how the RHC variants might lead to an increased susceptibility to melanoma development in response to UVB light exposure.
What did the research involve?
The research used a combination of studies in live mice, mouse and human skin samples, and human pigment cells to look at how UVB light affects the MC1R protein and how it interacts with other proteins.
One of these proteins (PTEN) suppresses the formation of tumours and is found at abnormally low levels in some melanomas. In particular, the research looked at whether the RHC variants of the MC1R protein behaved any differently to the “normal” (non-RHC) forms in response to UVB light.
What were the basic results?
The researchers found that when exposed to UVB light, the MC1R protein normally binds to the PTEN protein and stops it being broken down. However, the RHC variant forms of the MC1R protein did not bind to PTEN and could not stop it being broken down.
In skin pigment cells this led to another pathway being activated, which led to the cells prematurely “ageing” and no longer dividing. Premature ageing may sound bad, but this would normally stop the cells becoming cancerous.
However, if the cells also had another genetic mutation – which is found in nearly 70% of human melanomas – then the UVB-exposed RHC variant pigment cells developed cancerous properties (dividing in an uncontrolled fashion).
How did the researchers interpret the results?
The researchers concluded that their results further show that the normal form of MC1R acts as a tumour suppressor. They also say that the interaction between MC1R and PTEN in pigment cells is important in pigment cells’ response to UVB, and underlies the link between MC1R variants and melanoma.
The current research investigated the molecular pathways involved in the response of pigment cells to UV light exposure. It also looked at how this is affected in people with the variations in the MC1R protein that lead to red hair. The findings further our understanding of how these variants of MC1R may lead to a higher susceptibility to developing melanoma.
The mechanisms by which melanoma arises are likely to be complex, and the current research may only provide one piece of the puzzle.
A news story in May 2013 discussed other theories on how the MC1R variants may increase cancer risk.
Undoubtedly research in this area will continue. Researchers hope that better understanding of how cancers develop will help them to think of new ways they could treat them or prevent them.