The "UV tanning pathway" and melanoma

As it is summertime now, I must not be the only one who can’t wait to jump into the pool and give myself a tan. Bronzy cheeks and bodies are currently the big trend in the fashion industry. It also seems to be everyone of my friends’ dream and ultimate goal. However, have you noticed the fact that some people can easily get tans when some only get sunburns? If you happen to belong to the latter group, stop trying so hard to bathe in more sun, because you are also at higher risk of getting melanoma.

Melanoma is a type of skin cancer that develops from melanocytes - the cells that produce pigment in the skin. Melanoma only contributes a small proportion of all skin cancers but counts for the large majority of skin cancer deaths. In fact, it is highly associated with ultraviolet (UV) radiation, of which most exposure is due to direct sunlight and tanning beds. So before you get ready to dive into the sun, here is something you should know about the science behind the tanning process.

Two major aspects of our bodies take the leading role in this "UV tanning pathway" - skin cells and pigment cells (e.g. melanocytes). UV radiation first induces DNA damage within skin cells, which triggers the release of a special compound called alpha–Melanocyte-stimulating hormone (α-MSH). As suggested by its name, the hormone can stimulate the pigment cells by binding directly to the melanocortin 1 receptor (MC1R) on the cell surface. Stimulating the MC1R receptor starts the manufacturing process that produces melanin, the major ingredient of our tans.

This receptor protein is arguably the biggest player in the “UV tanning pathway” and is known to exist in different “flavors” (i.e. mutant variants) across each ethnic group. Different MC1R variants have distinct pigment-producing abilities, resulting in very dark or light skin. One of the most famous examples is red-headed individuals with very pale skin. One may immediately think of Ron (Harry’s best friend) in Harry Potter. Ron as well as the whole Weasley Family fall into this category. These individuals usually have “weaker” MC1R function than others - their pigment producing “factories” are not as efficient.

The MC1R variant that the Weasley Family share determines their red hair, fair skin, and also suggests that the family all have poor tanning ability, higher sunburn risk, as well as the highest risk of melanoma among all skin pigmentation types. Of course, the most straightforward explanation is that pale skin forms less of a shield against UV radiation than darker skin. Oddly enough, the MC1R variants of pale-skinned people also give rise to higher melanoma risk even without UV radiation, suggesting an additional vulnerability that can’t be protected by sunscreen alone.

Studies have suggested that additional mechanisms, such as defective DNA damage repair and increased oxidative stress (These can cause DNA damage) may be to blame, though further experiments are needed to figure out the details.  Something to note is that common active ingredients of most sunscreens (e.g. titanium dioxide and zinc oxide) can release oxidative free radicals on the skin. Interestingly, these free radicals may actually increase the risk of developing melanoma for this red-haired, pale-skinned group of individuals. Thus one theory in the skin cancer field actually questions the rationality of everyone to prevent melanoma by applying sunscreens regardless of his or her MC1R status.

At least for the pale-skinned folks, it is worthwhile to consider avoiding too much sun exposure (and the tanning bed). Instead, go for the false-tanning cosmetics if there is an insatiable craving for that sun-kissed glow.

Reference:
UV signaling pathways within the skin J Invest Dermatol. 2014 Aug; 134(8): 2080–2085.