Studies have revealed that drinking caffeinated beverages reduces one’s chances of developing some types of cancer, including UV-associated skin cancer. Now, researchers propose a possible mechanism for this observation—the inhibition of a DNA repair pathway that sensitizes cells to death after sun exposure.
The results of the new study appear in the Proceedings of the National Academy of Sciences, lend support to the idea that caffeine could be added to sunscreens to increase its protective effects.
Cancer epidemiologist Joanne Kotsopoulos of the University of Toronto, not involved in the research commented, “At the cellular level, they’re showing that caffeine is working in this way of inducing an apoptotic mechanism…It’s biologically plausible, and it has good implications” for potential skin cancer prevention strategies.
A 2007 study of nearly 94,000 women, for example, found that woman who drank caffeinated coffee on a daily basis had a 10 percent lower risk of non-melanoma skin cancer. Six or more cups of coffee a day translated to a 30 percent reduction in risk. Mouse studies have also confirmed the link, with both ingested and topically-applied caffeine lowering skin cancer rates in the animals. But exactly how the stimulant protected against cancer was unclear until now.
One possibility is the drug’s inhibition of ataxia telangiectasia and Rad3-related (ATR), a large protein kinase that senses incomplete DNA replication - often a result of DNA damage - and signals the cell to not divide. By inhibiting ATR activity, caffeine could make cells more likely to die in response to UV damage, preventing damaged cells from ever becoming cancerous.
To test this hypothesis, cancer biologist and dermatologist Paul Nghiem of the University of Washington Division of Dermatology examined mice that were sensitive to UV damage, and thus prone to skin cancer. Because knocking out ATR activity entirely would’ve killed the mice, Nghiem and his colleagues developed a transgenic mouse model with an additional, mutated copy of the protein. The mutated version competed with the wild type protein and effectively reduced ATR activity without eliminating it altogether.
Exposing the mice to UV radiation, the researchers found that it took transgenic mice about 3 weeks longer to develop skin cancer than their transgene-negative littermates. After 19 weeks of UV treatment, the transgenic mice had 69 percent fewer tumors than the controls. Furthermore, the tumors that the transgenic mice did develop were less likely to advance to the more serious form of the disease, squamous cell carcinoma (SCC).
The researchers also tested the skin cells from the mice in vitro, adding caffeine shortly after UV exposure. While caffeine caused the cells from the control mice to become sensitized to the radiation, increasing the rate of apoptosis, it had no effect on the cells that already had reduced ATR activity. “So it argues that caffeine is working on the same pathway as ATR,” Nghiem said.
“Eventually, if you treat them long enough, the mice will develop cancer so it is not 100 percent protection forever,” Allan Conney, one of the study's authors, said. “Really, with almost any carcinogen, eventually all the animals will develop tumors,” added Conney, who is director of the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers University in New Jersey.
Nghiem said, “Therefore adding it to sunscreens may make sense for two reasons—it’s directly a sunscreen, and completely independently, it has this effect on ATR.” “I think there’s good potential to keep investigating this,” Kotsopoulos said. “I mean, how easy would that be? To formulate [caffeine] into existing sunscreens as an additive?”
Alternatively, a drug other than caffeine that targets ATR may be used, said biophysicist Douglas Brash of Yale University’s School of Medicine. “Caffeine was an interesting historical way of discovering this mechanism,” he said, “but now that we know the mechanism…maybe we hunt for some other drug that’s more specific.” Given the results of the new study, such drugs may be able to be repurposed to fight skin cancer as well, Brash said.
Skin cancer is a common disease. According to Cancer Research UK, around 100,000 cases of non-melanoma were registered in the UK in 2008, and just under 12,000 cases of the more dangerous malignant melanoma. These cancers can be caused by over-exposure to ultraviolet light from the sun, which can damage the DNA of skin cells, leading to errors when the cells divide.
Jessica Harris, a health information manager at Cancer Research UK, pointed out that this study examined how caffeine affected genes when it was directly applied to the skin, rather than ingested. “It didn't look at the effects of drinking coffee, so doesn't tell us whether or not this could reduce the risk of skin cancer,” she said. “Studies looking at coffee consumption and cancer in large groups of people have provided mixed results,” she added. “Some have found that coffee drinking may slightly reduce the risk of certain types of cancer, but the evidence is not yet strong enough to be certain, and these effects tend to be seen among people who drink very large amounts.” The best way to reduce the risk of skin cancer, said Harris, “is to enjoy the sun safely, taking care not to burn by using a combination of shade, clothing and sunscreen.”
Dot Bennett, a professor of cell biology at St George's, University of London, said that any move to add caffeine or related molecules to sunscreens should be undertaken with care. “First one might want to check there is no adverse effect of caffeine on the incidence of other cancers, especially melanoma (pigmented skin cancer), which kills over four times as many people as [squamous cell carcinoma]. But caffeine lotion might promote tanning a little, since this family of molecules stimulates pigment cells to make more pigment.”
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