Overview of Environmental Skin Cancer Risks

Issues of Concern

Ultraviolet Radiation

Exposure to ultraviolet (UV) radiation from sunlight is widely recognized as the primary risk factor contributing to the development of skin cancer. This radiation is known to have damaging effects on the DNA present within skin cells. UV radiation, a part of the electromagnetic spectrum, exists in 3 forms: UVA, UVB, and UVC. Among these, UVA rays have the longest wavelength, which ranges from 320 to 400 nm. These rays are primarily responsible for photoaging, which is the breakdown of collagen and elastin in the skin due to UV damage. This damage leads to the formation of wrinkles and pigmentary changes. UVB rays, with wavelengths between 290 and 320 nm, primarily cause sunburn and skin cancer by damaging DNA and causing mutations in skin cells. UVC rays have a wavelength that falls below 290 nm and are effectively absorbed by the earth's atmosphere. These rays do not reach the surface significantly, as the ozone layer mainly blocks UVC rays.

UV radiation from the sun or artificial sources, such as tanning beds, penetrates the skin and directly damages DNA within cells. Pyrimidine dimers are specific DNA lesions formed by UV radiation, significantly when nearby thymine or cytosine bases in the DNA sequence are affected.[3] Although the body's repair systems attempt to fix these lesions, prolonged or repeated exposure can overwhelm this process, leading to the accumulation of DNA mutations within skin cells. Non-melanoma skin cancers are more commonly related to chronic UV exposure, whereas melanoma can result from intermittent intense sun exposure, often during childhood. Severe sunburns, especially during childhood or adolescence, are associated with a higher risk of developing melanoma.[4]

Given the substantial risk of skin cancer induction by UV radiation, identifying strategies to mitigate individual risk is essential. Clinicians should encourage patients to utilize sun safety practices, such as avoiding direct sun exposure between 10 AM and 2 PM when the UV index is highest, seeking shade, wearing sun-protective clothing to cover the skin, wearing a wide-brimmed hat and sunglasses, and using sunscreen. Clothing items labeled with the ultraviolet protection factor have been tested and shown to protect against UV rays. When choosing a sunscreen, patients should be encouraged to use a broad-spectrum sunscreen, which covers UVA and UVB rays, with SPF 30 or higher and reapply it every 2 hours.

Arsenic

Exposure to arsenic has been associated with an increased risk of skin cancer, with non-melanoma skin cancer representing the main focus of this connection. Arsenic, a naturally occurring element found in the soil and groundwater, can enter the body through various sources such as drinking water, food, and air.[5] High levels of exposure can occur in geological regions burdened with a high contamination rate or due to occupational or agricultural practices. The risk is significantly elevated in individuals with chronic exposure. Although public water systems are tested for arsenic levels, private wells are not regulated, and the responsibility for testing the water source falls on homeowners.[6] Chronic arsenic exposure can lead to hyperpigmentation and hyperkeratosis of the skin, with the most affected areas including the hands. Arsenic is a co-carcinogen because the substance increases the cytotoxicity and mutagenicity of UV radiation on cells.[7] As a result, individuals exposed to both arsenic and UV radiation are at a higher risk of developing skin cancer compared to those exposed to UV alone. Preventive measures against arsenic-induced skin cancer involve increasing public awareness of groundwater arsenic levels and the routes of entry into the body.

Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons are a group of chemicals that contain multiple fused aromatic rings. These hydrocarbons originate from the incomplete combustion of organic materials such as wood, coal, oil, and tobacco.[8] Consequently, polycyclic aromatic hydrocarbons are ubiquitous environmental pollutants found in various settings, including industrial processes, vehicle exhaust, and cigarette smoke. These hydrocarbons can be metabolized by enzymes in the body, resulting in the subsequent generation of reactive oxygen species. This process, in turn, contributes to oxidative stress by causing damage to DNA strands and cell membranes and a decrease in skin-protective antioxidants. The aryl hydrocarbon receptor plays a crucial role in the initiation and progression of skin cancer. This receptor governs inflammation and cell death induction by facilitating the toxic and biochemical impacts of air pollutants such as ozone, dioxins, and polycyclic aromatic hydrocarbons.[9]

Cigarette Smoke

Cigarette smoke contains numerous harmful chemicals and has been implicated in cancers affecting the respiratory, gastrointestinal, and genitourinary tracts. Evidence suggests a correlation between cigarette smoke and skin cancer. Cigarette smoking has been associated with an increased risk of squamous cell carcinoma, particularly on the lips, ears, penis, and vulva.[10] The most significant risk is found in heavy smokers and individuals with prolonged exposure. Quitting smoking not only lowers the risk of skin and respiratory cancers but also enhances cardiovascular health.

Immunosuppression and Medications Linked to Skin Cancer

Immunosuppression refers to the weakening of the immune system, which can hinder the ability to defend against infections and abnormal cell growth. Organ transplant recipients face an elevated risk of developing non-melanoma skin cancer, primarily due to the immunosuppressive medications they take to prevent organ rejection.[11] Following an organ transplant, recipients must take immunosuppressive medications to prevent the body from rejecting the transplanted organ. Although these drugs are essential for the survival of the graft, they weaken the body's immune response, making the system less effective at detecting and destroying cancerous cells. Moreover, skin cancers that develop in organ transplant recipients tend to be more aggressive, have a higher likelihood of recurrence, and are more likely to spread to other parts of the body.[12] These skin cancers may require more extensive treatment and have a poorer prognosis. Specific maintenance immunosuppressive agents include calcineurin inhibitors, such as cyclosporine; antiproliferative agents, such as azathioprine; mammalian target of rapamycin inhibitors, such as sirolimus; and corticosteroids, such as prednisone. Calcineurin inhibitors, such as cyclosporine, form the cornerstone of immunosuppressive therapy in patients with organ transplants. Cutaneous squamous cell carcinoma poses a significant challenge in association with these medications, presenting a risk 65 to 100 times higher compared to that in the general population.[13] Azathioprine is a well-documented medication known to increase the risk of cutaneous squamous cell carcinoma and, to a lesser extent, basal cell carcinoma.[14] Importantly, these medications are often used in combination, compounding the risk of carcinogenicity and increasing the likelihood of subsequent development of non-melanoma skin cancer.[15]

Other medications confer an increased risk of skin cancer, including hydrochlorothiazide, methotrexate, and tumor necrosis factor inhibitors. Hydrochlorothiazide is a diuretic primarily prescribed for high blood pressure. This medication has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma.[16] The exact mechanism remains unclear but appears related to photosensitizing effects, making the skin more sensitive to UV radiation and increasing the risk of sunburn. Methotrexate is an antineoplastic drug that inhibits the enzyme dihydrofolate reductase, which is necessary for cell division. The drug has been linked with an increased risk of both melanoma and non-melanoma skin cancers due to immunosuppressive and photosensitizing effects.[17] Tumor necrosis factor inhibitors are a class of medications known as biologic agents and are commonly used to treat rheumatologic diseases. Studies have shown an increased risk of developing non-melanoma skin cancers with the use of these medications.[18][19]

In addition to the above medications, many others are photosensitizing and, therefore, may pose an increased risk of skin cancer. Antibacterial agents, such as tetracyclines and sulfonamides; nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen; and antidiabetic medications, such as glipizide, have all been shown to increase the skin's sensitivity to UV light.[20][21]

Connecting Skin Damage with Climate Change

Shifts in global climate and weather trends, particularly the increase in the earth's average surface temperature, are closely linked to emissions of greenhouse gases and disruptions in the carbon balance caused by human activities. These anthropogenic activities encompass the combustion of fossil fuels, emissions of greenhouse gases from industrial processes, and deforestation, leading to a reduction in carbon-absorbing resources.[22] Furthermore, rising temperatures may alter human behavior, encouraging extended outdoor activities throughout a more significant portion of the year. This change in behavior, coupled with stratospheric ozone depletion, amplifies the skin's total UV exposure.[23] The damage inflicted on the skin due to UV radiation is contingent upon ambient temperatures, with elevated temperatures causing more harm at identical UV light levels.[24]

Clinical Significance

The most commonly diagnosed types of skin cancers are non-melanoma skin cancers, mainly basal cell carcinoma and squamous cell carcinoma. These less aggressive cancers outnumber melanoma cases, which is linked to higher mortality rates. Basal cell carcinoma often presents as pearly pink papules with rolled borders and telangiectasias, whereas squamous cell carcinoma presents as an erythematous, hyperkeratotic papule or plaque with central erosion. Melanoma typically appears as an asymmetric, darkly pigmented nevus with border irregularity and a diameter greater than 6 mm. Although non-melanoma skin cancers are less likely to spread, squamous cell carcinoma carries a higher risk of metastasis compared to basal cell carcinoma. However, the impact of these diseases should not be underestimated. Reported increases in the incidence and mortality of non-melanoma skin cancers are likely underestimated due to some cancer registries not mandating their reporting.[25]

From 1990 to 2019, male patients in the United States experienced higher rates of non-melanoma skin cancer incidence, prevalence, disability-adjusted life years, and mortality compared to their female counterparts. The mortality rate for males was 3.2 per 100,000, whereas for females, it was 1.4 per 100,000 persons. Although both melanoma and non-melanoma skin cancer incidence rates have increased, mortality rates have either remained stable or decreased. Between 2007 and 2011, the estimated cost of treating skin cancer in the United States reached $4.8 billion for non-melanoma skin cancer and $3.3 billion for melanoma, representing a significant portion of healthcare expenses.[26]

Numerous well-documented risk factors contribute to the development of skin cancer. These factors encompass skin exposure to UV radiation; early-life occurrences of severe sunburns; the utilization of tanning beds; exposure to chemicals, such as arsenic and polycyclic aromatic hydrocarbons; cigarette smoke; compromised immune systems; and genetic factors such as family history and personal history of multiple melanocytic nevi.[27] Among these risk factors, UV radiation is the primary causative agent.[28] Several factors likely contribute to the increased development in skin cancer incidence. Indeed, rising global temperatures associated with climate change and heightened exposure to UVB radiation due to stratospheric ozone depletion may play significant roles in this trend.[29] The connections between these factors have gained increased recognition, particularly in light of the well-established link between UV exposure and skin cancer pathogenesis. In addition, increased diagnostic suspicion and increased rates of screening biopsies have contributed to the rising incidence.[30]

Other Issues

Mohs Micrographic Surgery for Skin Cancer Management

Many treatment options are available to treat skin cancer, and Mohs micrographic surgery is a remarkable innovation that offers precise excision while preserving maximal tissue. This technique is commonly used for non-melanoma skin cancer and can also be used for rare, aggressive skin cancer types such as melanoma and Merkel cell carcinoma.

Mohs micrographic surgery is mainly indicated for high-risk skin cancers, tumors located near critical structures or in cosmetically sensitive areas, those with uncertain margins, and when a patient prefers this procedure over other options. High-risk skin cancers include those with large tumor sizes, aggressive histologic subtypes, and cancers resistant to prior treatments.[31] In addition, Mohs micrographic surgery is an excellent option for tumors located near vital structures such as the eyes, nose, or ears and in cosmetically sensitive areas such as the face, hands, and genital region.[32] Skin cancers with poorly defined margins, such as morpheaform or sclerosing basal cell carcinoma, may be more challenging to excise using conventional surgical methods completely.[33] Hence, Mohs micrographic surgery is a good option. Finally, patients often opt for Mohs micrographic surgery over other forms of treatment for their tumor removal due to its high cure rate and favorable cosmetic outcomes.

Enhancing Healthcare Team Outcomes

Interdisciplinary collaboration refers to the teamwork and coordination among healthcare professionals from different disciplines to deliver holistic and patient-centered care. In the context of skin cancer, this collaboration is vital due to the multifaceted nature of the disease and the diverse expertise needed for its prevention, diagnosis, and treatment.

Clinicians, including nurses and advanced practice providers, are at the forefront of patient care and play a crucial role in reducing the incidence of skin cancer. They frequently interact with patients and are well-positioned to educate them about the importance of skin cancer prevention and early detection. By equipping these healthcare professionals with knowledge about skin cancer's environmental risk factors, such as UV radiation exposure and the use of tanning beds, they can empower patients to adopt sun-safe behaviors and undergo regular skin examinations for early detection of suspicious lesions.

Furthermore, interdisciplinary collaboration extends beyond clinical settings to encompass public health initiatives aimed at reducing the overall burden of skin cancer on the population. Healthcare providers can engage in efforts to raise public awareness about the dangers of excessive sun exposure; promote the use of protective measures, such as sunscreen and protective clothing; and advocate for policies that support sun safety practices.

Interdisciplinary collaboration is essential for comprehensive skin cancer care. By leveraging the expertise of various healthcare professionals and engaging in collaborative efforts to educate and empower both patients and the broader community, healthcare providers can make significant strides in reducing the incidence and impact of skin cancer.