What is the Skin Cancer Risk in Vitiligo?

Skin Cancer Risk in Vitiligo

Vitiligo is a common condition that results in completely whitened areas of skin. This is due to a lack of pigment-producing cells called melanocytes in the areas that become white. Patients with vitiligo have an immune system that attacks the melanocytes in different parts of the skin creating visible white spots.[1] With extensive whitening of the skin, one might expect skin cancer to become more common. After all, lighter skinned individuals are at greater risk for skin cancer than darker skinned individuals. And we know that the pigment in the skin is important for absorbing the light from the sun, protecting our cells from damage. However, it turns out vitiligo patients do not have an increased skin cancer risk. In fact, they seem to be protected from skin cancer in the areas of skin affected!

Different types of skin cancer exist and older studies had mixed results regarding the lower risk of skin cancer in vitiligo patients. In this article, the different skin cancers are discussed, the evidence that supports the decreased skin cancer risk is described, and how vitiligo patients are somewhat protected from skin cancer is addressed.

Skin Cancer Types

Melanoma

Melanoma is a life-threatening skin cancer that develops from melanocytes found in the top layer of the skin. These are the same pigment-producing cells killed off in vitiligo. Melanoma is more common in lighter skinned patients and is more common in patients with a personal or family history of melanoma.[2]

Nonmelanoma Skin Cancers: Basal Cell & Squamous Cell Carcinoma

Nonmelanoma skin cancers include basal cell carcinoma and squamous cell carcinoma.[3] These cancers originate from two different cell types within the top layer of skin. Basal cell carcinoma is the most common type of cancer in the United States, while squamous cell carcinoma is the second most common. These cancers are typically caused by a long history of sun exposure. Patients who sunburn or tan often are at greater risk. For this reason, both basal cell and squamous cell are typically found in older patients after their skin has been exposed to the sun for decades.[3]

Decreased Risk of Skin Cancer in Skin Affected by Vitiligo

A lot of research has been done to show that the risk for both melanoma and nonmelanoma skin cancers is decreased in the skin affected by vitiligo. In a very large study, researchers looked at approximately 10,000 vitiligo patients and 26,000 individuals without vitiligo or other skin conditions.[4] The researchers looked at a computer database to compare the two groups’ histories of skin cancer diagnoses recorded by physicians in the past. This study showed that vitiligo patients had a 4-fold decrease in their risk of developing melanoma. Even when patients of the same age and gender were compared directly (to make the comparison more even), the study still found about a 3-fold decrease in risk.[4]

In another large study, 1300 vitiligo patients and 788 non-vitiligo patients were compared.[5] Questionnaires were sent to those with and without vitiligo and asked about skin type, skin cancer history, sun exposure history, and vitiligo history. Vitiligo patients were found to have a 3-fold lower risk of developing melanoma, similar to results from the study mentioned above. There were seven vitiligo patients that had a history of melanoma, but all of the melanomas occurred in the skin without vitiligo. Not a single melanoma developed on the vitiligo-affected, whitened skin.[5]

A much smaller study with 136 patients with vitiligo were evaluated with a set of standardized questions and a skin biopsy.[6] The study looked into the sun damage in vitiligo skin and the incidence of skin cancer. When examining the skin biopsies of these patients, there was little evidence of skin damage from sun exposure in vitiligo skin despite patient-reported childhood sunburns and other sun exposure.[6]

Light Therapy and Skin Cancer Risk in Vitiligo

Vitiligo is treated with many different therapies including steroids, calcineurin inhibitors, and light therapy.[7] Light therapy is exactly what it sounds like—patients go into a room with a special light that shines directly on their skin to treat their condition. Therapy comes in a variety of forms, but usually includes some form of UV light that the sun normally emits.

In light therapy the UV light is delivered in a more controlled and intense way compared to the sun. Since UV light from the sun is known to damage the skin and result in cancer over time,[8] researchers have looked at whether vitiligo patients treated with light therapy have an increased skin cancer risk.

In the larger study with over 10,000 vitiligo patients, researchers found that even in patients with a significant light therapy history, their risk of developing skin cancer was three times lower than patients without vitiligo or other skin conditions.[4]

One older light therapy once used for vitiligo is called PUVA (psoralen and ultraviolet A). A smaller study looked at the long-term effects of UV light therapy on vitiligo patients.[9] The study included 12 patients who had received treatment during the previous 9 years consisting of an average of 84 individual PUVA treatments over 2 years. The study found no increased risk of skin cancer or even skin damage from the therapy.[9] This was a very small study and additional research is needed to support the findings, but the results agree with other studies that show that the affected skin in vitiligo seems more resistant to UV damage.

Explaining How Vitiligo-Affected Skin is Protected

With multiple studies showing vitiligo virtually protects against skin cancer, the question remains: how is it possible? The answer lies in the details of how vitiligo occurs in the first place. This includes free radicals, the overreaction of the immune system and differences in patients’ genetic makeup.

Vitiligo skin may be more resistant against free radicals

Cancer cells are driven by the production of free radicals, very small molecules that damage most normal cells. There are two antioxidant enzymes that get rid of free radicals throughout our bodies called superoxide dismutase and glutathione peroxidase. Both of these are individually associated with a decreased risk of nonmelanoma skin cancer since they decrease free radicals thereby deterring cancer cells from growing. Studies have shown an increase in superoxide dismutase and glutathione peroxidase in vitiligo. This supports the idea that in areas where vitiligo is present, cancer is absent due to decreased oxidative stress to melanocytes controlled by increased SOD and GP in the area.[10]

Immune system proteins

Cancer cells can also be killed by special cancer-killing proteins and cells in our immune system. The immune system produces two proteins, IL-1 and TNF-α, important for preventing or killing cancer cells including skin cancer. IL-1 and TNF-α also stimulate the production of superoxide dismutase and glutathione peroxidase which decrease free radicals. These immune system proteins combat cancer through stimulating the immune system, killing cancer cells, and decreasing the formation of free radicals to reduce the development of cancer cells. IL-1 and TNF-α are overly abundant in skin affected by vitiligo. With increased amounts of these proteins, it makes sense why vitiligo patients would have better defenses against skin cancer.[11]

Genetics: differences in the TYR gene

Genetics is the word that describes the information passed down from parents to children that makes up each cell in the body. This information is what we call DNA. Every person’s genetics, their DNA, is different giving rise to different looks, behaviors, or disease. Although there are many ways skin cancer can develop, one way it can develop is when our skin cell DNA is changed by UV rays from the sun. Additionally, patients with vitiligo have a specific change in a part of their genetics which predisposes them to developing the condition.

Vitiligo is considered an autoimmune condition wherein the body attacks melanocytes. Tyrosinase is an enzyme that creates melanin, the pigment inside the melanocytes that gives us our skin color. TYR is a segment on our DNA responsible for creating tyrosinase. Basically, TYR makes tyrosinase which, in turn, makes melanin (pigment) in melanocytes.

Studies have found differences in the TYR gene in vitiligo patients making researchers believe that this difference flags the melanocytes to be more easily attacked by the immune system.[12] The thought is this: if a patient has vitiligo, their TYR site makes the immune system attack the melanocytes and perhaps other skin cancer cells. While this is bad in vitiligo, it may be good for protecting against skin cancer!

Table 1. Biological differences between vitiligo and non-vitiligo patients

Protein/enzyme

Biological Action

Increased or decreased in vitiligo?

Outcome

Risk of skin cancer?

Superoxide dismutase[10]

Antioxidant metalloenzyme that reduces superoxide radical toxicity

Increased

Less oxidative stress to melanocytes

Decreased

Glutathione peroxidase[10]

Antioxidant enzyme that converts peroxides to water

Increased

Less oxidative stress to melanocytes

Decreased

IL-1[11]

Proinflammatory cytokine

Increased

Stimulate SOD and GP

Decreased

TNF-a[11]

Proinflammatory cytokine

Increased

Stimulate SOD and GP

Decreased

402R TYR protein[12]

Encodes Tyrosinase which leads to melanin biosynthesis

Increased

Increased immune surveillance of neoplastic melanocytes

Decreased

 

Do People With Vitiligo Not Need to Worry About UV Light?

Although vitiligo patients have a decreased skin cancer risk, they still need to worry about UV light like everyone else. Patients have a lower risk of developing skin cancer, but that does not mean they will never get skin cancer. There is still a risk, so patients should protect their skin from UV light. Additionally, the risk for skin cancer is really only decreased in the areas of skin with vitiligo present. This means the remainder of the normal skin is still susceptible to skin cancer and should be protected. Protection from UV light includes sunscreen with an SPF of 30 or more, sun protective clothing (hats, pants, long-sleeves), and avoiding intense sunlight by seeking shade or staying inside during the hours between 10 a.m. and 4 p.m. Vitiligo patients can feel comfortable that they have some internal protection from skin cancer, but can increase their protection even more with good sunlight protection!

* This Website is for general skin beauty, wellness, and health information only. This Website is not to be used as a substitute for medical advice, diagnosis or treatment of any health condition or problem. The information provided on this Website should never be used to disregard, delay, or refuse treatment or advice from a physician or a qualified health provider.

References

  1. Ezzedine K, Eleftheriadou V, Whitton M, et al. Vitiligo. Lancet.2015;386(9988):74-84; PMID: 25596811 https://www.ncbi.nlm.nih.gov/pubmed/25596811.
  2. Chen T, Fallah M, Forsti A, et al. Risk of Next Melanoma in Patients With Familial and Sporadic Melanoma by Number of Previous Melanomas. JAMA Dermatol.2015;151(6):607-615; PMID: 25671687 https://www.ncbi.nlm.nih.gov/pubmed/25671687.
  3. Kim RH, Armstrong AW. Nonmelanoma skin cancer. Dermatol Clin.2012;30(1):125-139, ix; PMID: 22117874 https://www.ncbi.nlm.nih.gov/pubmed/22117874.
  4. Paradisi A, Tabolli S, Didona B, et al. Markedly reduced incidence of melanoma and nonmelanoma skin cancer in a nonconcurrent cohort of 10,040 patients with vitiligo. J Am Acad Dermatol.2014;71(6):1110-1116; PMID: 25242557 https://www.ncbi.nlm.nih.gov/pubmed/25242557.
  5. Teulings HE, Overkamp M, Ceylan E, et al. Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo: a survey among 1307 patients and their partners. Br J Dermatol.2013;168(1):162-171; PMID: 23136900 https://www.ncbi.nlm.nih.gov/pubmed/23136900.
  6. Schallreuter KU, Tobin DJ, Panske A. Decreased photodamage and low incidence of non-melanoma skin cancer in 136 sun-exposed caucasian patients with vitiligo. Dermatology.2002;204(3):194-201; PMID: 12037447 https://www.ncbi.nlm.nih.gov/pubmed/12037447.
  7. Zhang Y, Mooneyan-Ramchurn JS, Zuo N, et al. Vitiligo nonsurgical treatment: a review of latest treatment researches. Dermatol Ther.2014;27(5):298-303; PMID: 25041437 https://www.ncbi.nlm.nih.gov/pubmed/25041437.
  8. Mancebo SE, Wang SQ. Skin cancer: role of ultraviolet radiation in carcinogenesis. Rev Environ Health.2014;29(3):265-273; PMID: 25252745 https://www.ncbi.nlm.nih.gov/pubmed/25252745.
  9. Vussuki E, Ziv M, Rosenman D, et al. [Long-term effects of PUVA therapy on Israeli patients with vitiligo]. Harefuah.2006;145(7):483-485, 552, 551; PMID: 16900734 https://www.ncbi.nlm.nih.gov/pubmed/16900734.
  10. Dammak I, Boudaya S, Ben Abdallah F, et al. Antioxidant enzymes and lipid peroxidation at the tissue level in patients with stable and active vitiligo. Int J Dermatol.2009;48(5):476-480; PMID: 19416376 https://www.ncbi.nlm.nih.gov/pubmed/19416376.
  11. Feily A, Pazyar N. Why vitiligo is associated with fewer risk of skin cancer?: providing a molecular mechanism. Arch Dermatol Res.2011;303(9):623-624; PMID: 21830160 https://www.ncbi.nlm.nih.gov/pubmed/21830160.
  12. Jin Y, Birlea SA, Fain PR, et al. Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. N Engl J Med.2010;362(18):1686-1697; PMID: 20410501 https://www.ncbi.nlm.nih.gov/pubmed/20410501.
 
 
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