Everybody’s Free To Wear Sunscreen…And Prevent Skin Cancer

Our last article discussed using sunscreen to help protect skin against damaging UV radiation. When used properly, sunscreen prevents sunburn and sun-induced skin aging, and protects from skin cancer. Studies have shown that sunscreen use reduces the incidence rate of squamous cell carcinoma (SCC) and melanoma, but currently no evidence supports a protective role against basal cell carcinoma (BCC).

While some people, including supermodel Gisele Bundchen, believe sunscreen is dangerous (she declared “I cannot put that poison on my body”) experts such as The Skin Cancer Foundation and the American Academy of Dermatology—and even Cosmopolitan magazine—disagree with her and other skeptics.

A large, randomized controlled trial examined the effect of daily sunscreen use on the development of skin cancers. Researchers followed 1621 Australians from 1992-2006. From 1992-1996, participants were randomly placed in a group and instructed to either use the study-provided broad spectrum SPF 16 sunscreen daily on face, arms, neck and hands, or to continue personal discretionary use of sunscreen. At the 2004 follow up, researchers noted that the daily sunscreen use group had a 35% rate reduction in the incidence of SCC (considering all SCCs that appeared throughout the entire study). However, the incidence of BCC was not statistically different between the two groups. More recent studies corroborate these results.

US Senator and 2008 Republican Presidential Candidate John McCain has had multiple melanomas removed. Other political figures have battled skin cancer, including former Presidents Jimmy Carter (metastatic melanoma) and Bill Clinton (BCC), and former First Lady Laura Bush (SCC).

In 2006, researchers followed up again, this time looking for melanoma. The overall incidence rate of melanoma was 50% less in the sunscreen intervention group than the discretionary use group (out of approximately 800 people in each group, 11 people in sunscreen group and 22 in the control group developed melanoma). It should be noted that these results had borderline statistical significance, with a P value of 0.051 (P = 0.05 is the accepted cutoff for significance). This essentially translates to a 5.1% probability of these findings being due to chance, rather than to the actual sunscreen intervention. Also, there was a 73% lower rate of invasive melanoma in the sunscreen group. Although there was no significant difference in number of melanomas diagnosed at the prescribed intervention sites, it is possible that sunscreen use reduced the risk, as participants in the sunscreen intervention group reported more frequent use of sunscreen over the whole body after the intervention terminated.

Although these results are not the most compelling, they nonetheless point to a protective role of sunscreen. Many factors may contribute to a less than straightforward outcome. First, the sunscreen intervention was in adults and lasted 4.5 years. Melanoma and BCC are thought to result from both long term sun exposure and intense, intermittent episodes (sunburns), whereas SCC is mainly caused by cumulative UV exposure (both natural and indoor tanning bed). Furthermore, blistering childhood sunburns are a risk factor for melanoma. One study that examined sunscreen use in children found a significant protective benefit. Regular use (applied any time sun exposure would exceed 30 min) of a broad-spectrum SPF 30 sunscreen over a 3-year period resulted in significantly fewer newly developed moles, the number of which is a risk factor for melanoma.

Second, participants in the non-sunscreen intervention group continued their discretionary use of sunscreen. No trial in humans could ever prohibit sunscreen use or provide a placebo for ethical reasons. Therefore, perfectly delineating the protective effect of sunscreen is difficult.

Many questionnaire-based studies that rely on participants’ memory of sunscreen use suffer from recall bias. Some of these studies showed no benefit of sunscreen for melanoma prevention but memory limits the reliability of these results. The bottom line is that sunscreen protects from UV radiation, a known human carcinogen.

The skin consists of two layers, the dermis and epidermis. The epidermis contains a variety of cell types, including squamous cells, basal cells and melanocytes. These are the sources for squamous cell carcinoma, basal cell carcinoma and melanoma, respectively.

UV radiation is implicated in up to 90% of nonmelanoma skin cancers, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Mutations consistent with UV radiation were also found in the genomes of melanoma tumors; UV radiation is thought to be responsible for the majority of melanoma. Whereas SCC and BCC are more frequent, melanoma is more often fatal. While UV radiation is the single most important risk factor for skin cancer, it’s worth noting that it is not responsible for all skin cancers. Aside from environmental carcinogens, cancer can arise due to a person’s genetics (familial effect) or random mutations.

Acral melanoma is a type of skin cancer not caused by UV radiation and is genetically distinct from UV-induced cutaneous malignant melanoma. Bob Marley’s acral melanoma metastasized and ultimately claimed his life.

UVA radiation primarily damages the components of skin cells by generating reactive oxygen species, or ROS. These highly active molecules can cause single-strand breaks in the DNA or crosslink DNA to protein, resulting in mutations or improper functioning. Both UVA and UVB can cause a more significant type of DNA damage called pyrimidine dimers, where two adjacent pyrimidine nucleotides (the “C” and “T” of DNA; the “A” and “G” are purines) fuse together. Because the higher energy UVB is absorbed directly by DNA, UVB can cause other modifications that compromise the integrity of DNA, leading to instability of the genetic code.

Indeed, the cell has repair mechanisms to fix pyrimidine dimers and other errors, but sometimes the very genes encoding the repair mechanisms are mutated. UV-induced DNA damage can result in highly characteristic mutations in critical genes, for example in the tumor suppressor gene p53. As the “guardian of the genome”, the p53 protein is involved in directing the repair of mutations and guiding the cell through its controlled death pathway, called apoptosis. Mutations in p53 are thought to be among the first steps in development of non-melanoma skin cancer. Formation of malignant melanoma is more complicated and not fully understood.

Yes, p53 has its own superhero persona. That’s how cool (and significant) it is. Image by Susanne Harris.

Cells that carry mutations in p53 proliferate uncontrollably, a hallmark of cancer. In some cases, the immune system will recognize malignant cells as a threat and effectively eliminate them. However, UV radiation is also known to suppress the immune system by at least two mechanisms. One is by diminishing the production of antigen-presenting cells, which engulf foreign-looking cells and display an alert to activate the immune system). The other is by inducing the production of an immune suppressive cytokine, interleukin-10. Additionally, some skin cancer cells display proteins on their surface that prevent the immune cells from killing them. Thus, in addition to mutations in key genes, immune suppression and immune evasion contribute to the development of skin cancer.

Even the mutant Wolverine wears sunscreen! In this Instagram post, Hugh Jackman urged his fans to use sunscreen. He became a fervent sunscreen proponent after having a BCC removed from his nose.

Contributed by: Julia van Rensburg, Ph.D.
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van der Pols JC, Williams GM, Pandeya N, Logan V, & Green AC (2006). Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 15 (12), 2546-8 PMID: 17132769

Lee TK, Rivers JK, & Gallagher RP (2005). Site-specific protective effect of broad-spectrum sunscreen on nevus development among white schoolchildren in a randomized trial. Journal of the American Academy of Dermatology, 52 (5), 786-92 PMID: 15858467

Koh HK, Geller AC, Miller DR, Grossbart TA, & Lew RA (1996). Prevention and early detection strategies for melanoma and skin cancer. Current status. Archives of dermatology, 132 (4), 436-43 PMID: 8629848

Leiter U, & Garbe C (2008). Epidemiology of melanoma and nonmelanoma skin cancer--the role of sunlight. Advances in experimental medicine and biology, 624, 89-103 PMID: 18348450

Brenner M, & Hearing VJ (2008). The protective role of melanin against UV damage in human skin. Photochemistry and photobiology, 84 (3), 539-49 PMID: 18435612

Into The Fire: Sun Protection From A To B

In the last month, Jessica Alba has made splashes across media headlines, but not for her latest role in a Hollywood blockbuster. The Honest Company, which she founded in 2011, has been charged with two lawsuits filed by consumers. Both lawsuits cite ineffective sun protection by the Honest Company sunscreen, and countless online images of sunburned children and adults appear to support these allegations. The failure of the sunscreen highlights a need for better education regarding sunscreen use and sun exposure. So let’s start with the one currently under fire.

Jessica Alba’s recent role has been protecting everyday people from allegedly harmful chemicals found in standard household products and cosmetics; her Honest Company offers “all natural” substitutes.

The Honest Company sunscreen contains only one active ingredient, zinc oxide, a naturally occurring mineral known for its UV reflecting properties. (The second lawsuit cites false advertisement for claims of using only “natural” substances when apparently synthetic components were included. And although zinc oxide exists naturally as zincite, it is likely that the zinc oxide used in sunscreen is synthesized in the lab). Zinc oxide is an effective broad-spectrum sunblock, protecting against both UVA and UVB radiation, but adequate concentrations must be used. If you’ve ever felt like your sunscreen just wouldn’t rub in, you’ve likely used zinc oxide, as its large particles leave a white, opaque residue many sunscreen users dislike.

The Hoff boasted, “Beyond its entertainment values, 'Baywatch' has enriched and in many cases helped save lives.” Perhaps he was referring to the prevention of nose-specific skin cancer, as he may have inspired others to liberally, but very specifically, apply chalky zinc oxide sunscreen to this body part.

Indeed, last year, the Honest Company sunscreen contained 20% zinc oxide, and many consumers complained of the undesirable aesthetic characteristics. This year, the Honest Company more than halved the zinc oxide concentration, reducing it to 9.3%. Although this change may have improved the sunscreen’s aesthetic properties, it most certainly reduced its ability to effectively block the sun’s UV radiation.

Zinc oxide, and its cousin, titanium dioxide, comprise inorganic sunscreen components. These particles reflect most of the radiation, but can absorb some of the energy. Newer sunscreen formulations typically use the nanoparticle version of these components, reducing the pasty appearance produced by the older, larger particles. Many sunscreens mix these minerals with the other class of sunscreen components:  organic molecules. Organic in this sense means “carbon-containing”, and refers to synthetic molecules made of carbon backbones. In addition to the inorganic components, some organic sunscreen molecules also provide broad-spectrum protection. However, the chemical structure of other molecules absorbs narrower wavelengths, so these are more effective when mixed with other narrow-spectrum or broad spectrum ingredients. The goal of mixing sunscreen components is to provide a broad-spectrum, photo-stable sunscreen that has acceptable aesthetic properties and increases the safety and effectiveness of the sunscreen.

These compounds are the most commonly used sunscreen ingredients. Avobenzone, ecamsules, and anthrilates absorb UVA radiation. Homosalate, octisalate, and octinoxate (also known as octyl methoxycinnamate) absorb UVB rays. Oxybenzone, octocrylene, and the inorganic particles zinc oxide and titanium dioxide filter both UVA and UVB radiation. Most sunscreens use a combination of these components to provide adequate broad-spectrum UV protection.

Forbes’ contributor David Korr noted that perhaps the formulation contributed to the sunscreen failure. The sunscreen label directed users to shake well before using, likely to redistribute to zinc oxide particles throughout the lotion. However, it is possible that many people skipped this step, resulting in some very heavy and greasy applications and other light and useless applications. So, formulation and proper consumer use indeed influence the effectiveness of sunscreen.

Other common misuses of sunscreen are applying too little or failing to reapply often enough. The FDA tests sunscreen at 2.0-2.2 mg of sunscreen per square centimeter of skin. To adequately cover an entire average-sized adult human body, at least 1.0 ounce (2 tablespoons or the volume of a shot glass), is needed.

In 2011, the FDA mandated higher standards for sunscreen labeling, requiring full compliance by the end of 2012. Under the new regulations, only sunscreens containing ingredients that absorb both UVA and UVB radiation can be classified as “broad-spectrum”. A sunscreen product with SPF (Sun Protection Factor) 15 or greater can state that it protects against all forms of sun damage, including sunburn, premature skin aging, and skin cancer. Those with SPF 2-14 can only state that they have been shown to prevent sunburn. Additionally, “waterproof” can no longer be used; rather if appropriate, labels can specify “water-resistant” with the length of time (either 40 or 80 minutes) before reapplication is needed. Keep in mind that these changes did not remove other sunscreens from the market, but merely mandated what they can claim.

Avoiding painful sunburns requires proper use of sunscreen—most importantly, actually using sunscreen whenever you are exposed to the sun for extended periods of time.

SPF refers to the amount of UV radiation filtered out by the sunscreen. Thus, a sunscreen user with a proper application of SPF 15 sunscreen is exposed to 1/15^th of the sun’s harmful radiation. This suggests that SPF 15 sunscreen imparts a 15-fold increase in the length of time one can spend in the sun without getting burned. However, the FDA and Mayo Clinic recommend reapplying sunscreen at least every 2 hours and more often if swimming, sweating, or toweling off. Another way SPF is explained is that SPF 15, 30, and 50 protect from 93%, 97%, and 98% of UV radiation, respectively. Keep in mind that SPF refers to protection against only UVB radiation; there is no numerical rating of UVA protection.

UV radiation is more energetic than visible light, but not as energetic as X-rays; thus, it penetrates the top layers of skin, but not beyond that.

It was previously thought that UVA radiation was harmless; however, recent evidence shows that UVA does indeed contribute to tanning/sunburn, premature skin aging, and skin cancer. UVA comprises 90-99% of the UV radiation that reaches the Earth’s surface, whereas UVB radiation accounts for 1-10%. The stratospheric ozone layer filters out most of UVB and all of UVC radiation. The longer wavelength, lower energy UVA radiation can penetrate clouds, glass, and the skin’s dermal layer. Shorter, higher energy UVB rays do not significantly penetrate glass, but penetrate the epidermis and cause the majority of sun-induced skin damage.

UVA rays can penetrate deeper into the skin, reaching the dermis layer, whereas UVB penetration is limited to the epidermis.

The recent changes in sunscreen labeling were prompted primarily by new information on UVA radiation and the increasing incidence rates of skin cancer. In a future article, I will discuss how UV radiation promotes or causes skin cancer. Until then, remember that the highest concentration of UV radiation is 10 am – 4 pm, April through October. But that doesn’t mean you shouldn’t take precautions at other times of day or other times throughout the year. Sun protection should be a year-round commitment, keeping in mind that water, snow, and concrete can reflect sunlight. In addition to properly using sunscreen, wearing protective clothing and avoiding peak sunlight will protect your skin from UV radiation.

Contributed by: Julia van Rensburg, Ph.D.

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Shah P, & He YY (2015). Molecular regulation of UV-induced DNA repair. Photochemistry and photobiology, 91 (2), 254-64 PMID: 25534312

Narayanan DL, Saladi RN, & Fox JL (2010). Ultraviolet radiation and skin cancer. International journal of dermatology, 49 (9), 978-86 PMID: 20883261