Different Causes of Skin Cancer

Skin cancer is one of the most common forms of malignancies that has continually been increasing in prevalence. Currently, between 2-3 million cases of non-melanoma skin cancer and 132,000 cases of melanoma-based skin cancer occur globally each year. Typically, skin cancer develops from increased ultraviolet (UV) radiation impact from prolonged sun exposure. However, even with the implementation of various precautionary measures to safeguard the skin from UV radiation, skin cancer can still occur on concealed skin. From a biological perspective, it is understood how UV radiation causes skin damage at a cellular level. However, to completely interpret the origins of skin cancer, the contributing geographical factors must be considered as well.

The skin is the largest organ of the body, safeguarding us from pathogens while also taking a central role in thermoregulation (regulation of body temperature). Skin has three layers—the epidermis, dermis, and hypodermis. The epidermis, which is the outermost layer, boasts our skin tone and provides a waterproof barrier to preserve essential water and electrolytes molecules from diffusing out of the body. Beneath the epidermis is the dermis, consisting of the sweat glands, vasculature, nerve endings, and hair follicles that protect the innermost layers of the skin and allow for sensation. The hypodermis works alongside the body’s vasculature (mostly the arteries) for optimal thermoregulation. It includes connective tissue and subcutaneous fat that acts as a cushion to protect the body’s visceral organs from physical trauma.

Humans require sunlight to synthesize vitamin D, which is essential for the optimal function of the musculoskeletal system and many other bodily activities. However, excessive sun exposure damages DNA that controls the function of skin cells. Excited oxygen molecules hitting DNA may cause the transversion of DNA base pairs, ultimately causing a mutation. When DNA is altered, it cannot effectively control skin growth, resulting in rapid cell growth. Eventually, the accumulation of abnormal cells may form a malignant tumor, leading to skin cancer.

Skin cancer is classified into two major groups: melanoma and keratinocyte (non-melanoma). Melanoma occurs due to the abnormal growth of melanocytes, which are cells located in the epidermis, and is an extremely aggressive form of cancer. Melanocytes produce the pigment melanin, which is responsible for the production of an individual’s unique skin tone. Though melanoma occurs less frequently than keratinocyte cancers, it is more fatal because of its ability to rapidly spread to surrounding organs if not treated quickly. The prominent risk factor for melanoma is high, intermittent UV radiation exposure. Due to the irregularity of UV exposure, melanoma can often go unnoticed for a substantial amount of time where it rapidly proliferates and soon spreads into nearby vasculature, increasing the risk of metastasis.

On the other hand, keratinocyte cancers, which include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are associated with long-term UV exposure. BCC occurs due to the abnormal proliferation of basal cells, which are found at the bottom of the epidermis. Basal cells generate new skin cells and push old skin cells towards the surface where they die and shed off. BCC most commonly occurs on the head or neck, as these places are especially prone to high levels of sun exposure. SCC starts with the abnormal growth of squamous cells, the thin, flat cells that make up the epidermis. Similar to BCC, SCC can develop on the head or neck; however, SCC also commonly occurs on any part of the body, including on the back of the hands, inside the mouth, and on the lips or genitals. Individuals who utilize tanning beds often are at a very high risk of acquiring SCC and tend to be affected by it relatively early in life.

The distribution of skin cancer in the population is largely affected by geographical location. For instance, individuals who live near equatorial areas, locations with a depleted ozone layer, are prone to excess UV exposure, which increases the risk of developing skin cancer due to prolonged hours of sunlight and reduced ozone protection from UV rays. The same applies to those living on elevated plateaus or high altitudes, as the increased atmospheric pressure in these places often results in there being fewer clouds. Clouds are generally able to block UV rays to some extent, so having less cloud cover overhead logically raises the risk of surplus exposure. Patchy clouds may also increase UV radiation by reflecting it from their edges. Thin, wispy clouds, too, can redirect UV rays, thereby increasing ambient radiation and thus raising the regional risk level for skin cancer.

As the sun rises in the morning hours, the amount of available UV radiation increases as the sun reaches its angular peak at a certain point in the day. Although UV radiation is not dependent on temperature, behavioral changes may still affect skin cancer risk in warmer areas: those residing in such places may spend more time outside or wear attire that exposes more skin. It is also important to note that the disease is not necessarily mitigated with cooler temperatures. In fact, many individuals from chilly regions mistakenly fail to take precautionary measures, such as wearing hats or applying sunscreen, to protect themselves from UV rays.

Beyond the dangers posed by UV radiation, recent studies have shown that air pollution, which already has known impacts on cardiovascular and respiratory health, may also be detrimental to human skin. Excessive emissions from non-renewable energy sources such as coal, natural gas or crude oil are prominent sources of air pollution. When used, they release many harmful particulates into the air. Direct exposure to particulates such as volatile organic compounds, ozone, nitrogen dioxide, and sulfur dioxide is proven to deteriorate skin health. These pollutants are usually inhaled, although they can alternatively penetrate the skin through a cut or exposed site. There are 4 identified mechanisms that air pollutants potentially use to harm skin—the production of free radicals, disruption of skin barrier by initiation of inflammatory cascade, activation of aryl hydrocarbon receptors, and changes to skin microflora.

Particulate matter, which includes free radicals, induces skin barrier dysfunction and provokes the formation of reactive oxygen species, both directly and indirectly. Ozone, for example, is a particulate with unstable characteristics causing it to be highly reactive—it can directly target the skin’s surface and oxidize with molecules of the epidermis. Moreover, particulates increase the secretion rate of sebum, which, in turn, decreases the creation of vitamin E. Since vitamin E is the predominant antioxidant in the skin, reducing its production worsens skin condition and promotes inflammation. In response to such tissue injury, the body starts a chemical signaling cascade that stimulates immune responses to heal impacted tissues. The immune system sends leukocytes to eradicate pollutants within the body, activating the process of leukocyte chemotaxis and further bringing about local inflammation. As a specific example, neutrophils, a type of white-blood cell, produce pro-inflammatory cytokines, such as Tumor Necrosis Factors (TNFs), which stimulate the vasodilation of blood vessels and increase blood flow. For individuals with existing malignancies, this severely increases the risk of metastasis, as it prompts migration and transport of cancerous cells along the bloodstream and to distant organs. Furthermore, chronic inflammation can be dangerous, as it can lead to inflammation-associated carcinogenesis. In this case, immune cells create highly reactive molecules, such as oxygen and nitrogen which damage DNA. Through cytokines such as TNFs, immune cells also promote the formation of tumors from the proliferation of cells.

The Aryl Hydrocarbon Receptor (AHR), a protein present in humans, binds with organic pollutants, polycyclic aromatic hydrocarbons (PAHs), and environmental carcinogens to mediate their biological and toxic consequences. Despite this, studies show that activation of AHR increases one’s susceptibility to SCC, and that the protein is a prognostic factor in the development of Merkel cell carcinoma and melanoma. Provoked by the inflammatory cascade in skin from oxidative stress, the binding of organic pollutants to AHR increases skin cancer risk and poses a big threat to an individual’s health.

Air pollutants also negatively impact skin microflora, which consist of the diverse microorganisms including Staphylococcus, Micrococcus, and Dermabacter. These microbes help ward off pathogens and enhance immune response. According to a study by He et al., there was a 50% decrease in residual skin microflora in the presence of ozone. Such dramatic changes can allow pathogenic strains of Staphylococcus, Streptococcus, and other bacteria to colonize the epidermis, perhaps leading to serious inflammatory issues, such as cellulitis. Particulates can also settle down on the skin and block pores, creating an anaerobic environment that is favored by some pathogens.

Overall, various environmental factors—most notably high altitudes, latitudinal location, and air pollution—contribute to the global distribution of skin cancer. As well, particulates from fossil fuel emissions can bind to the skin and cause unwanted immune responses, elevating the risk of malignancies and metastasis in humans. In recognizing these risks, national governments can use their power to help reduce the prevalence of skin cancer in their respective countries. While skin cancer continues to affect many worldwide, the condition can be fought by spreading public awareness about preventive measures, which imperative to benefit the overall health and well-being of our society.

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