Tuesday August 16 2011
This is very early-stage research, conducted in genetically modified mice
“Applying caffeine to the skin in sunny weather may protect against a type of skin cancer”, BBC News has reported today.
This news is based on a scientific study examining why caffeine consumption has previously been linked to lower rates of some types of cancer, including non-melanoma skin cancer. Caffeine is known to block the workings of an enzyme called ATR, which is normally used by the body to sense and help repair DNA damage. So researchers examined what happened when they blocked the enzyme in genetically modified mice.
These mice had also been engineered to be susceptible to skin cancer, allowing scientists to determine how blocked and functioning forms of ATR affected rates of non-melanoma skin cancer in the mice. Mice with inactive ATR in their skin cells were found to take longer to develop cancer and had fewer tumours than mice with normal ATR after exposure to UV light. This seemed to be due to damaged cells automatically dying when ATR was not functioning.
Although this work sheds light on certain cellular processes involved in the formation of skin cancer, its results are of little direct relevance to preventing skin cancer, particularly as the study was done in mice and because they had been genetically modified to have an extremely high risk of skin cancer.
Given the early stage of this line of study, it will take much further laboratory and human study to tell whether a caffeinated sunscreen could have any potential.
Where did the story come from?
The study was funded by the US National Institutes of Health, and it was conducted by a number of medical and research organisations. The study was published in the peer-reviewed scientific journal, Proceedings of the National Academy of Sciences USA (PNAS).
All national newspapers that reported the research covered it well, generally making it clear that this was experimental lab work in mice. While a number of newspapers have tentively discussed the potential of a using caffeinated sunscreen, it should be noted that these are based on comments in the discussion section of the research paper rather than the study testing any sunscreen. In their paper, the researchers had said their results “suggest the possibility that topical caffeine application could be useful in preventing UV-induced skin cancers”.
Also it should be noted that while newspapers have referred to caffeine potentially protecting against skin cancer in their reports, studies have only demonstrated caffeine’s potential effects against the rarely-fatal, non-melanoma form of skin cancer, and not the highly aggressive malignant melanoma form of the disease.
What kind of research was this?
This was a laboratory-based study, performed in mice. Previous studies have found associations between consumption of caffeinated drinks and a reduced risk of UV-associated non-melanoma skin cancers in humans and mice. Previous research has also performed tests applying caffeine to the skin of mice that were genetically susceptible to cancer after exposing them to UV light, which led to a reduction in cases of squamous cell carcinoma, a type of slow-growing skin tumour that is rarely fatal.
Caffeine affects several proteins in the cell, including an enzyme called ATR which senses DNA damage and blocks certain cellular processes in order to allow affected DNA to be repaired. This study used genetically modified mice to determine whether blocking the action of ATR affected UV-induced non-melanoma skin cancer. Animal research such as this is often used in the early-stage investigation of such biological theories.
What did the research involve?
The researchers used mice that had been genetically modified to express a non-functioning form of ATR in their skin. These mice were crossed with mice that had the gene for the condition ‘xeroderma pigmentosum C deleted’, a rare human disease where an inability to produce a protein called XPC prevents UV damage from being repaired, thereby causing tumours to develop after a relatively short period of UV exposure. Although xeroderma pigmentosum is a rare genetic disease, invasive squamous cell cancers that develop in people without xeroderma pigmenosum often show an inability to produce the XPC protein.
The researchers analysed the UV-response of skin cells in these mice with inactive ATR and susceptibility to skin tumours due to lacking XPC. They made the same analysis in control mice with normal ATR that lacked XPC. The researchers then looked at tumour formation in the mice after they were exposed to UVB light three times a week for 40 weeks.
What were the basic results?
After checking that modified mice were producing an inactive form of the ATR enzyme, the researchers isolated skin cells from the mice and from control mice with normal ATR. They found that proteins normally targeted by ATR were no longer activated in mice producing the inactive form of the enzyme after UV exposure. They also found that proteins targeted by a similar enzyme called ATM were unaffected. It has already been found that human skin cells with damaged DNA and blocked ATR functions undergo ‘programmed cell death’. The mouse cells with inactive ATR were found to behave in a similar manner after UV exposure.
The researchers then looked at tumour formation in the mice after UV light exposure three times a week for 40 weeks. Control mice started developing tumours after 12 weeks of UV treatment. Mice with inactive ATR in their skin cells had delayed tumour development, with a three-week delay in time of onset of the first tumour. At any given time point the average number of tumours in mice with inactive ATR was significantly lower than in control mice. Mice with an inactive form of the ATR enzyme had 69% fewer tumours after 19 weeks of UV treatment. However, by the end of the study all the mice had at least one tumour.
Both the control mice with active ATR and the mice with inactive ATR developed that same type of skin cancer. However, the mice with inactive ATR developed fewer invasive squamous cell carcinomas.
How did the researchers interpret the results?
Their results showed that genetically inhibiting (blocking) the function of the ATR enzyme causes damaged mouse cells to die after UV exposure, and that mice with inactive ATR in their skin cells take longer to develop cancer and have fewer tumours. Based on this, the researchers conclude that “ATR inhibition in skin is well-tolerated and suppresses UV-induced tumour development”. They say that, “combined with the extensive epidemiologic data linking caffeine intake with decreased skin cancer development, these findings suggest the possibility that topical caffeine application could be useful in preventing UV-induced skin cancers”.
This study used genetically modified mice to determine whether blocking the action of the ATR enzyme affected UV-induced non-melanoma skin cancer. ATR is an enzyme which senses DNA damage and blocks the cell cycle to allow DNA to be repaired. ATR is one of the enzymes in the cell that is inhibited by caffeine, and from these results it would seem that damaged cells with inhibited ATR will tend to automatically die rather than try to repair themselves after UV exposure.
Previous studies have found that caffeine can reduce the risk of some types of cancer, including non-melanoma skin cancer such as squamous cell carcinoma. In this study, inactive ATR had a similar effect to caffeine on skin cells after UV damage. The researchers conclude that this may suggest that caffeine’s UV protective effect, documented in previous studies, is due to ATR inhibition.
The researchers conclude that their findings (together with those of previous studies) “suggest the possibility that topical caffeine application could be useful in preventing UV-induced skin cancers”. However, it should be remembered that this is very early stage research, which has analysed tumour formation in genetically modified mice, and which has very limited implications. For example, the mice in this study were genetically engineered to model the rare genetic disorder of xeroderma pigmentosum – a condition in which people will quickly develop skin tumours after very low levels of UV exposure, and are hence not representative of the general population. Also, caffeine has so far only been demonstrated to have some potential for preventing non-melanoma squamous cell skin cancer. Squamous cell cancer, though also caused by UV-light exposure, is a slow-growing cancer that can usually be completely cured using surgical removal. It is very different from malignant melanoma skin cancer, a very aggressive cancer that can spread very quickly and carries a high mortality risk unless treated early.
Given the current level of study, and given that caffeine has been only demonstrated to have an effect against non-melanoma skin cancer, much further laboratory and human study would be needed before it is known whether a caffeinated sunscreen could have any potential.