UV+Exposure,+Skin+Type+and+Cancer

toc =__Research Question __=

Our project aims to examine the effects of UV exposure, voluntary and involuntary, in different skin types. In our research we hope to compare the rates of skin cancer in these different levels of exposure to see if a correlation between skin type and elevated levels of melanoma exists. Also, we hope to analyze the varying expression of melanin-producing genes (that give skin pigmentation) in the basal layer of the skin in order to determine the function or role that melanocytes play in the three main types of skin cancer.

=__Introduction __=

UV Radiation
The sun gives off energy in three main of wavelegnths: visible light, infrared light, and UV light. There are 3 types of UV radiation: UVA, UVB and UVC. The ozone layer protects the earth against most UV radiation. It does not protect against UVA and sometimes UVB can get passed it and reach the earth. The level of UV light depends on the time of year, day, and location. Levels are highest at noon in the summer in places close to the equator. Also, 95% of UV radiation on earth is from UVA light. UVA radiation penetrates deeper into the skin, reaching the dermis layer whereas UVB light penetrates into the epidermis. This damages the DNA of cells in the epidermis and dermis and that can lead to mutations which can lead to skin cancer. Even though the UVA light penetrates deeper, the UVB light is more mutagenic. Cells try to protect themselves from DNA damage from the UV rays by donating melanin from the melanocytes to keratinocytes. This is the process that makes you tan. winkwhite

Skin Types
There are 6 different skin types. People that are type 1 always burn and never tan. They are at high risk for melanoma. People that are type 2 almost always burn and rarely tan, similar to type 1. People with type 3 skin sometimes burn and sometimes tan. People who are type 4 tan easily and are less likely to burn. People who are type 5 tan easily and rarely burn and type 6 are dark skinned people who do not burn. No matter what type of skin you have, you are still at risk for skin cancer; some have a higher risk than others. To identify you're skin type, you can use the Fitzpatrick Testto score yourself. This test uses genetic disposition, tanning habits and reaction to sun exposure to figure out skin type.

Check out this video for an introduction to skin cancer! media type="youtube" key="qavf-OP5XMM" height="315" width="420" align="center"

=__Types of Skin Cancer __=

Melanoma is the most agressive and dangerous type of skin cancer. Simply put, Melanoma develops when UV radiation causes damage to skin cell DNA which can trigger mutations that can lead to tumor formation and metastasis. Most of these mutations occur in the melanocytes. Normally, melanocytes produce melanin, which produces the skin's natural pigmentation or color. Furthermore, melanin cells absorb sunlight when skin is directly exposed acting as the body's natural sunscreen. When the DNA damage causes the melanocytes to act in a disregulated fashion, cancer can arise. Most often, melanoma originates in the basal layer of the skin and they resemble moles or some kind of skin spotting. It is notorious for its resistance to cancer therapies by resisting apoptosis. It does this by reprogramming proliferation and survival pathways.
 * Melanoma **

As can be seen in the figure, melanoma penetrates the epidermis basal layer, and enters the dermis layer of skin. Melanomas are typically black or dark brown although some cases have reported red, purple, and even blue spotting.


 * Warning Signs for Melanoma- The ABCD's **



The ABCD's of melanoma are a way to personally assess any skin moles or pigmentation in order to determine if it is cancerous or not. The figure  below shows pictures of what a cancerous pigmentation can look like based on the ABCD's warning signs.

 A-Asymmetry  If you draw a line through this mole, the two halves will not match.

 B-Border  The borders of an early melanoma tend to be uneven. The edges may be scalloped or notched.

 C-Color <span style="font-family: Arial,Helvetica,sans-serif;"> A number of different shades of brown, tan or black could appear. A melanoma may also become red, blue or some other color.

<span style="font-family: Arial,Helvetica,sans-serif;"> D-Diameter <span style="font-family: Arial,Helvetica,sans-serif;"> Melanomas usually are larger in diameter than the size of the eraser on your pencil.

<span style="font-family: Arial,Helvetica,sans-serif;">.

<span style="font-family: Arial,Helvetica,sans-serif;"> **<span style="font-family: Arial,Helvetica,sans-serif; font-size: 130%;">Squamous Cell Carcinoma (SCC) ** =<span style="font-family: Arial,Helvetica,sans-serif;"> = <span style="font-family: Arial,Helvetica,sans-serif;">This is probably the most common form of skin cancer. It is basically the uncontrolled growth of skin cells from the upper layer of the skin (epidermis). They often look like red patches, sores, or warts. Bleeding and scabbing are common as can be seen in the figure. It is usually caused by cumulative exposure to UV radiation over time, usually the course of a lifetime. If allowed to grow, it can be deadly because it can penetrate the basal skin layer. They can occur on all areas of the body, but are commonly found in areas that are exposed to the sun.

<span style="font-family: Arial,Helvetica,sans-serif;"> Some of the risk factors for SCC include : <span style="font-family: Arial,Helvetica,sans-serif;"> **<span style="font-family: Arial,Helvetica,sans-serif; font-size: 130%;">Basal Cell Carcinoma (BCC) ** <span style="font-family: Arial,Helvetica,sans-serif;"> Basal Cell Carcinomas are another very common type of skin cancer. It battles SCC for the most common type of skin cancer. These tumors arise in the basal layer of the skin but do not penetrate it. Usually look like sores, patches of open skin, pink skin growth, shiny bumps, or scars. It is usually caused by limited intervals of intense UV exposure or cumulative exposure over longer periods of time. It is not really life threatening because it doesn't penetrate the basal layer. It rarely spreads to other parts of the body. <span style="font-family: Arial,Helvetica,sans-serif;">PANCEAPLUS
 * Having light-colored skin, blue or green eyes, or blond or red hair
 * Long-term, daily sun exposure
 * Age
 * exposure to x-rays
 * chemical exposure

=__<span style="font-family: Arial,Helvetica,sans-serif;">Exposure to UV Radiation __= <span style="font-family: Arial,Helvetica,sans-serif;">Generally speaking, the idea is easy, the less exposure to UV radiation, the better. More UV exposure causes more DNA damage which makes a person more prone to cancer.This DNA damage is what provides the "crispy" tan that so many people strive for. The p53 protein is responsible for releasing melanocyte stimulating hormones when it senses any DNA damage to the skin from UV exposure. <span style="font-family: Arial,Helvetica,sans-serif;"> The p53, however, also is the suppressor gene that is most commonly mutated in the body, most likely because of the constant UV exposure (although this is our speculation). Mutations or deregulation of the p53 gene can lead to skin cancer because of the lack of stress response and lack of normal p53 function.This production of melanocytes is what gives skin the "darker" pigment. Tanning is a form of stress response from the skin, and the DNA damage intermediate from tanning exposure, is the same as an intermediate that can lead to cancer cells.

<span style="font-family: Arial,Helvetica,sans-serif;"> UV light damages cellular DNA by initiating a reaction between two molecules of thymine to form a dimer. As more dimers are formed, the risk for an incorrect repair in the DNA increases. This leads to its inability to function normally and it may become cancerous. When the cells are damaged by UV rays, the G1 phase is prolonged and it takes longer for the damaged DNA to be repaired .This is because there is a restriction point in this stage to make sure the DNA is intact before moving to the S phase. The p53 protein promotes DNA repair proteins and initiates apoptosis if it the damage cannot be fixed. When p53 is mutated, its ability to carry out its functions decreases and the dimers are not fixed and the cell replicates with the overlooked mutation. This is what leads to cancer.

<span style="font-family: Arial,Helvetica,sans-serif;"> **<span style="font-family: Arial,Helvetica,sans-serif; font-size: 130%;">In-Voluntary Exposure **

<span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 11px; text-align: justify; vertical-align: baseline;">Table 1: Relationships of personal sun exposure with risks of BCC, SCC and melanoma <span style="font-family: Arial,Helvetica,sans-serif;">In-voluntary exposure can include outdoor jobs or recreational activities that take place outdoors. The table above was taken from a study titled The Epidemiology of UV Induced Skin Cancer. Having a history of sunburns shows a linkage with melanoma. There is a 191% higher risk for melanoma for people with a history of sunburns. However, this does not mean you are 191% more likely to get melanoma if you have a history of sunburns, it means that the odds increase by 191% from the starting baseline of the odds of getting melanoma. Occupational exposure creates a higher likelihood of squamous cell carcinoma than other types of exposures. Occupational exposure also creates a higher risk for squamous cell carcinoma compared to basal cell carcinoma and melanoma. There is a 164% increase in the odds of getting squamous cell carcinoma from occupational exposure. Interestingly, occupational exposure has the weakest relationship to melanoma, with a 86% increase in odds .Melanoma occurs in melanocytes and people that have been working outside most likely have more melanin because of cumulative exposure and this protects from mutations to occur in the melanocytes which would lead to melanoma. <span style="font-family: Arial,Helvetica,sans-serif;"> Squamous cell carcinoma occurs in the basal layer and is caused by cumulative exposure overtime, so it makes sense for this to have the strongest relationship with occupational exposure. This table was a good resource in showing the rates of cancer for the more common types of exposure that a person goes through everyday.
 * ~ Type of exposure ||~ BCC ||~ SCC a ||~ Melanoma ||
 * < Total ||< 0.98(0.68–1.41) ||< 1.53(1.02–2.27) ||< 1.20(1.00–1.44) ||
 * < Occupational ||< 1.19(1.07–1.32) ||< 1.64(1.26–2.13) ||< 0.86(0.77–0.96) ||
 * < Non–occupational or “intermittent” ||< 1.38(1.24–1.54) ||< 0.91(0.68–1.22) ||< 1.71(1.54–1.90) ||
 * < Sunburn at any age ||< 1.40(1.29–1.51) ||< 1.23(0.90–1.69) ||< 1.91(1.69–2.17) ||

<span style="font-family: Arial,Helvetica,sans-serif;"> **<span style="font-family: Arial,Helvetica,sans-serif; font-size: 130%;">Voluntary Exposure **

<span style="font-family: Arial,Helvetica,sans-serif;"> The most common form of voluntary exposure to UV radiation is through laying out in the sun unprotected (commonly known as "tanning") or using tanning beds or other form of "tanning devices." In recent years, tanning devices have become the fastest growing risk factor related to skin cancer. Voluntary exposure through tanning beds, etc has become "popular" and tanning salons and businesses are continuously targeting younger teens and women. Studies however, have concluded that the earlier one starts using indoor tanning devices, the more likely they are to get cancer at an older age. A study titled Adverse Effects of Ultraviolet Radiation from the Use of Indoor Tanning Equipment: Time to Ban the Tan concludes that the use of indoor tanning devices is highly associated with an increased risk of skin cancer. The article notes that many other studies have shown that almost all kinds of extended UV exposure can lead to DNA damage, whether a burn is seen or not. The effects of UV radiation on the skin, especially though tanning devices, are clear and frankly scary. The effects include melanoma as well as immunosuppression, photoaging, burns, wrinkles, photodermatoses, cataracts, and uveal melanomas. There are an increasing number of studies that link melanoma with the use of tanning beds. The International Agency for Research on Cancer conducted a study that found that melanoma risk increases significantly if tanning devices are used before the age of 35. Another British study showed that there is an increase in melanoma cases in young women. About 25% of cases of English young women with melanoma can be attributed to indoor tanning. The study however, did not explicitly mention a correlation with skin type. However, it can be inferred that since the amount of radiation in tanning beds is increased to minimally four times the amount of radiation from the, most skin types will react in a more uniform matter. Furthermore, the increased radiation at such a close level can obviously have much more extreme consequences. The authors advise that indoor tanning be regulated at a federal level in order to prevent the increased heath risk that indoor tanning entails. A complete ban for minors is also advised. The regulation and prevention of indoor tanning devices can protect the public from preventable cancers and other effects caused from the prolonged exposure to UV radiation.

<span style="font-family: Arial,Helvetica,sans-serif;"> ** Exposure and Skin Type? **

<span style="font-family: Arial,Helvetica,sans-serif;"> A study done in the year 2000, titled Melanocortin-1 Receptor Polymorphisms and Risk of Melanoma: Is the Association Explained Solely by Pigmentation Phenotype? investigates relationship of the melanocortin-1 receptor (MC1R) genotype to cutaneous malignant melanoma (CMM) risk, controlled for skin pigmentation phenotype. The MC1R, a G protein–coupled receptor with 7 transmembrane-spanning domains, plays a key role in determining the type of melanin (eumelanin vs pheomelanin) that is produced within melanocytes <span style="font-family: Arial,Helvetica,sans-serif;">. <span style="font-family: Arial,Helvetica,sans-serif;"> This study, by Palmer, et al. follows the occurrence of MC1R in an Australian populated sample group, and the relationship of the sample group to other common risk factors such as skin, hair, eye color, freckling, and nevus count. They found that hair color and skin type had the strongest connection to the MC1R variants that were analyzed. The study concludes that the effect of the MC1R variants that were found do have an effect on CMM which is partly mediated via the pigmentation of the phenotype and that, "these alleles may also negate the protection normally afforded by darker skin coloring in some members of the white population".

<span style="font-family: Arial,Helvetica,sans-serif;"> Of particular interest for this project were the results based on skin type or skin pigmentation. <span style="font-family: Arial,Helvetica,sans-serif;"> They found that one of the most prominent skin related risks was an increased number of moles. A high number of moles shows a complex relationship with other pigmentary characteristics and it was hinted that an increased number of moles is commonly found on fair skinned people. Having over 50 moles is considered a risk factor. An exception to this are red headed people who seem to have lesser numbers of moles despite the fair skin. Red headed people however, commonly get more freckles. In order to test for skin type/ color, the frequency of the MC1R allele was determined in 5 variants. The figure above shows the results of the study based on skin type broken down into three basic categories; fair, medium, and brown. The study evaluates the hypothesis that, "the most parsimonious explanation for the increased incidence of melanoma in individuals with either red or fair hair and with fair skin centers on their inability to increase melanin levels in the skin in response to high exposure to UV light". The information found that the frequencies of the MC1R variants did vary according to skin color.

<span style="font-family: Arial,Helvetica,sans-serif;"> So how does this relate back to skin type? There is no article that explicitly says that one skin type is more likely to get skin cancer than the other because that isn't completely true. All types of skin have the possibility of developing skin cancer depending on many factors including environment, exposure, family genetics, etc. However, many studies like the one cited above find direct correlations between lighter skin colors and higher risk of melanoma. A supplement to the Journal of the American Academy of Dermatology published last year, provides the most current melanoma statistics in the U.S. This supplement, titled Melanoma Surveillance in the United States was released in conjunction with the CDC last year and it provides the most comprehensive reports and statistics on melanoma up to this date. While they don't provide information directly on skin type, they provide a lot of information based on race/ethnicity which can be correlated to skin type. Most races have a distinct skin type or color based on their evolutionary background. Specific levels of melanin in skin can be associated to different races or ethnicity.

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<span style="font-family: Arial,Helvetica,sans-serif;"> The two tables above show the epidemiological and mortality rates of melanoma in the US between 2004 and 2006. This data supports the idea that fair skinned people, those that have higher levels of phaeomelanin, show the higher rates of melanoma and death while those with darker skin, those with higher levels of eumelanin, show lower occurrence and death rates. The difference between phaeomelanin and eumelanin is further discussed below.

=__<span style="font-family: Arial,Helvetica,sans-serif;">Melanin Producing Genes __= <span style="font-family: Arial,Helvetica,sans-serif;">Human skin pigmentation/color mainly depends on the concentration and distribution of melanin chromophores. Melanin is synthesized in melanosomes (membrane bound organelles) within melanocytes (specialized cells) that supply pigment "packets" via dendritic processes to surrounding epidermal cells. Melanin is synthesized as two, separate and distinct types; eumelanin and phaeomelanin. Eumelanin is a brown or black pigment, while phaeomelanin is with red or yellow pigmentation. The ratio of eumelanin to phaeomelanin determines visible characteristics, but also photoprotective and cytotoxic properties. Phaeomelanin has been found to generate oxidative stress which results in photosensitivity rather than photoprotection but with little cytotoxicity. On the other hand, eumelanin has a slightly more elevated level of cytoxicity, but a substantial increase in photoprotection. Of the two pigments, eumelanin is dominant in both epidermal fraction volume and perceived color which makes it the primary photo-protective molecule in human skin.

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<span style="font-family: Arial,Helvetica,sans-serif;"> A study conducted by Matts et al. worked to measure the levels in eumelanin in skin cells in vivoand relating the data to analytically determined eumelanin concentrations in non-exposed skin from subjects of the Fitzpatrick skin types I-VI. In order to do this, a new measurement device known as SIAscopy (spectrophotometric intracutaneous analysis) was used <span style="font-family: Arial,Helvetica,sans-serif;">.

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<span style="font-family: Arial,Helvetica,sans-serif;"> The figure to the left shows examples of staining of epidermal melanin in three of the different Fitzpatrick skin types. In the figure, part a represents type I skin, part b represents type IV skin, and part c represents type VI skin. The increasing levels of melanin pigmentation can clearly be seen in this figure.

<span style="font-family: Arial,Helvetica,sans-serif;"> The results of the study clearly indicated that there is a correlation between the eumelanin values produced by both contact and non-contact SIAscopy techniques as well as the analytical values for melanin for the same are of human skin. This conclusion was found in all six of the Fitzpatrick skin types. It was found that SIAscopy could be a helpful method of tracking melanin specific diseases as well as the tracking of photodamage endpoints, etc.

<span style="font-family: Arial,Helvetica,sans-serif;"> In this case, I found this article helpful in the sense that it showed exactly what melanin is, its function in protecting the skin, and how it is distributed in the skin. It also went in depth to explain that even though darker skinned people have more melanin, they are not necessarily free from getting skin cancer. In the study, melanin values over skin types I-IV increased incrementally. There was a large step increase to type V and an even bigger increase to type VI.

<span style="font-family: Arial,Helvetica,sans-serif;"> <span style="font-family: Arial,Helvetica,sans-serif;"> So basically, melanin is the main protecting factor in our skin. These cells are what absorb the UV radiation that hits our skin at any time in order to protect from DNA damage. Eumelanin, which is associated with the darker pigments, seems to absorb a little better than phaeomelanin, associated with lighter pigmentation. Also, it is constantly seen that phaeomelanin cells are not as numerous as eumelanin cells. This being the case, it becomes easier to see why it is often said that lighter skinned persons can be more susceptible to bad burns and skin cancer.

=__<span style="font-family: Arial,Helvetica,sans-serif;">So Does Skin Color Really Matter? __= <span style="font-family: Arial,Helvetica,sans-serif;"> No matter the color of their skin, everyone can get skin cancer. But, skin color does affect the level of risk for skin cancer one has. As mentioned, skin pigment depends on the amount of melanin produced by melanocytes. Melanin absorbs UV light and has antioxidant and radical scavenging properties. It scatters or absorbs UV light which limits its penetration into the epidermis. The more eumelanin produced, the darker the skin color and the more phaeomelanin produced the lighter the skin color. Darker skin types are less likely to get skin cancer because they have more melanin which has more photoprotective properties. In fact, people with fairer skin are 70% more likely to develop skin cancer than those with darker skin [40].

=__<span style="font-family: Arial,Helvetica,sans-serif;">Protection from UV Radiation __= <span style="font-family: Arial,Helvetica,sans-serif;"> Ways to protect yourself from UV radiation include covering up in clothes so that you don't expose your skin, stay in the shade, wear sunscreen,wear a hat and UV blocking sunglasses. Contrary to popular belief, dark colored clothing protects more than light colored clothing. Loose fitted is better then tight fitted because it allows for a more space between the clothes and skin for the light to penetrate through.There are special kinds of clothes with UPF (ultraviolet protection factor) that you can buy which limit UV penetration through the fabric [41]. Sunscreen has SPF that can help protect against UV rays. For good protection, one should use sunscreen with an SPF of 15 or higher and it should be applied to the skin 10-15 minutes before exposure. Also, some sunscreens protect only against UVAs but others can protect against both. Some of the active ingredients form a protective film on the skin which absorb UV radiation before it can penetrate the skin and the others reflect UV light [42]. The important thing about sunscreen is that you need to continuously re-apply throughout the day. This should be about every 2 hours or after swimming or sweating [43]. Hats can be work for protection as well. The best kind of hats for protection are those that are tightly woven, so not straw hats. Also, they should have a rim to provide shade to your face, ears and neck. Sunglasses can also be worn to protect the eyes from the UV rays; they should block both UVA and UVB rays. วิงค์ไวท์

=__<span style="font-family: Arial,Helvetica,sans-serif;">Conclusions __= <span style="font-family: Arial,Helvetica,sans-serif;">Exposure to UV rays can cause skin cancer. UVA and UVB can reach Earth and UVA is more common but UVB is more dangerous. The levels of this exposure can vary with skin type, geographic location and time. Different skin types have varying skin cancer risks; generally the whiter you are, the higher the risk. The darker you are, the more melanin in your skin which protects against UV rays by scattering the light or absorbing it. Melanoma is the most dangerous type of skin cancer and originates in the basal layer of the epidermis. Basal cell carcinoma is the most common form of skin cancer and it the least dangerous; it occurs in the basal layer but does not penetrate it. Squamous cell carcinoma occurs in the upper layers of the epidermis from cumulative sun exposure. UV rays can cause mutations in DNA and an example of this is a mutation in the p53 gene which when functioning normally, suppresses tumors. One of the worst ways to promote this is indoor tanning because it exposes the skin to higher levels of UV rays than plain sunlight. To protect yourself from UV rays and to lower your risk for cancer, cover your skin when exposed to sunlight, wear hats and sunglasses and most importantly wear sunscreen!