For those of us living in the Southern Hemisphere, December is seen as the official start of summer. It is also the point at which all the usual fear-mongering around sun exposure and skin cancer ramps up. Whilst I have no doubts that excessive ultraviolet radiation can be a factor in the overall risk for developing various forms of skin cancer, I don’t believe that it is the linear factor that we have perhaps been lead to believe it is. In other words, I think there is more to the risk equation than just how much time you spend in the sun.
The human body is constantly trying to balance itself against stressors, both internal and external, that are breaking the body down, and its ability to build itself back up (which can be overdone if there isn’t a sufficient hand brake on those systems). A recent paper suggests that, when it comes to suffering damage from ultraviolet radiation, humans might have a distinct time of the day where we can best withstand that stress and repair the damage, perhaps with implications as to when we expose ourselves to the sun and when we might choose to minimise that exposure.
While UV radiation has the ability to cause lesions to DNA which, if unrepaired, have the ability to become carcinogenic, humans also have the ability to repair this damage by effectively cutting out the damaged DNA segments. In people who have hereditary mutations in the genes that code for this repair mechanism, there is a 5000-fold increase in skin cancer rates.
Researchers have recently identified a protein that is critical in the role of damage-recognition – xeroderma pigmentosum group A (XPA). XPA is a rate-limiting factor in the repair sequence and is seemingly controlled by the body’s internal circadian clock. As such, the activity of this repair protein has a distinct rhythmicity. You can perhaps see where this is going. If XPA is needed to repair DNA damage caused by UV radiation, but it is only produced in the body during certain times of the day due to circadian rhythms, perhaps there is an optimal time of the day where you can match the two factors up?
To test this, the researchers used a mouse model. Mice, however, are nocturnal, compared to the diurnal rhythms of humans. Their findings with the mice;
In mouse skin there is more DNA replication and less repair in the morning and less replication and more repair in the evening. Because UV-induced skin cancers arise from mutagenic replication of epidermal keratinocyte DNA, the same UV dose is more carcinogenic in early morning hours than when given in the early evening hours.
Understandably, being a nocturnal creature, the mice’s skin isn’t adapted to receiving large UV radiation doses during the day and repairing the damage that such a dose might cause…
…mice exposed to UVR in the early morning hours are more likely to develop skin cancer than those receiving the same dose in the evening hours because of a poor repair rate, and therefore, avoiding sunlight exposure in the morning hours will likely reduce cancer risk.
So how might this knowledge translate to humans? Well at this point, it hasn’t been tested on humans or a model analogous to us, so it is all relatively theoretical at present…
Mice are nocturnal and humans are diurnal animals and, therefore, the core circadian clock and their outputs exhibit opposite phases. On the basis of this well-established fact, we predict that humans will have a higher rate of repair in the morning and would be less prone to the carcinogenic effect of UVR in the morning hours and it might be advisable for humans, to the extent possible, to restrict their occupational, therapeutic, recreational, and cosmetic UVR exposure to the morning hours.
We note that this is a deductive conclusion based on our findings in mice reported in this paper and the evidence that humans have a robust circadian clock in their skin, which is antiphase to the mouse clock and with the peak xpa transcript around 7:00AM.
On the basis of the differences in circadian rhythm patterns between mice and humans, and that the key protein for repair, XPA, hits its peak expression in humans at around 7:00am, it seems to make reasonable sense that we have evolved with the capacity to head out into the morning sunshine to undertake our chores with our defences set to full power. I note my experience of tropical countries is that the locals get out and about in the morning and tend to take shelter from the heat and the sunlight later in the afternoon.
From the standpoint that we want to balance out exposure to the sun to optimise our vitamin D production without over-exposing ourselves to ultraviolet radiation and risk overwhelming our defences, and thinking about how ancestral populations living in tropical regions may have structured their day, it would seem reasonable to conclude that sun exposure across the morning, and perhaps through to the early phase of solar noon, may offer us the best health returns at the lowest risk (allowing for the fact that the above deduction is yet to be tested directly in humans). This type of advice might be more user-friendly than a blanket ban on sun exposure by the cancer society fun police.
Of course, this means that the opposite may also hold true. Spending time sunbathing/bedding in the afternoon may be a maladaptive behaviour from an evolutionary standpoint, and may increase our skin cancer risk. If a skin cancer lesion does occur, all we get is a statistical reinforcement of the sun = skin cancer meme, and a complete lack of fidelity around the actual mechanism.
I note from the above paper, this line from the authors;
…DNA damage and repair are two of the multiple factors that impact cancer development.
Leaving aside the specifics of the multiple factors, we effectively have this sort of equation going on… skin cancer development risk = [DNA damage - DNA repair]. This leaves us a few areas to focus on to mitigate our risk. The Cancer Society focuses heavily and almost exclusively on the DNA damage factor, with their strategy to mitigate this being the likes of don’t go in the sun, or if you do, cover up with clothing, hats, glasses, and/or sunscreen. And of course, all of these are behavioural strategies where we place external physical barriers between our skin and the sun. We forget that we have internal defences, surely bolstered by how we might shape our internal environment through the likes of the food we eat. What sort of skin defence might we expect by eating a low nutrient, pro-inflammatory diet?
Accepting the fact that a degree of damage will occur, how well are we geared to undertake repairs? Do you have a diet rich in anti-inflammatory agents, antioxidants, cholesterol, immunomodulators? I can’t help but thinking that by living as close to being in line with one’s evolutionary biology as is possible in our modern environment, that we are automatically strengthening the repair side of the equation, leaving us less prone overall to developing skin cancers. This might be further enhanced by paying attention to our natural rhythms – including our circadian rhythms and those that track with the seasons.
I’ve written previously that, despite my fair skin, I have tended to get less sunburn since eating a paleo diet. I’ll now be more conscious of the time of day I get the bulk of my exposure from now on too.