Skin Cancer

Skin cancer refers to uncontrolled, abnormal cell growth occurring on the skin. There are various types of skin cancer, each arising from a different type of skin cell. As a result, the different skin cancer subtypes vary with respect to their signs, severity, and treatment options. The three main types of skin cancer are Basal cell carcinoma (BCC), Squamous cell carcinoma (SCC), and Melanoma, with BCC and SCC collectively referred to as nonmelanoma skin cancer (NMSC).^[1]

The main signs of skin cancer will be changes to the appearance of the skin, with some variation depending on the type of skin cancer present.^[1][2]

• Basal cell carcinoma: BCCs are typically skin-colored bumps that are often shiny and translucent. BCCs usually occur on the face (e.g., nose, ears, and lip) and neck as well as other areas with past exposure to ionizing radiation (e.g., sunlight). Bleeding and scabbing is a common sign of BCC.

• Squamous cell carcinomas: SCCs are typically pink to red-colored bumps. The affected skin can be scaly and appear inflamed. As with BCCs, SCCs most commonly occur on the face, neck, and other areas with past exposure to ionizing radiation. SCCs are often preceded by red, scaly areas of skin known as actinic keratoses.

• Melanoma: Melanomas are usually brown to black-colored lesions, resembling a mole, though they can also be pink papules. These lesions are generally asymmetrical, with irregularly-shaped, poorly-defined borders. Melanomas also tend to grow over time, often becoming larger than 6 mm in diameter (roughly the size of a pencil eraser). On the skin of chronically sun-exposed areas (e.g., the face), a melanoma subtype known as lentigo maligna may resemble a large sun spot (i.e., a flat patch of darker skin, also known as a liver spot, an age spot, or solar lentigo).

The first step towards a skin cancer diagnosis is visual examination of the skin by a medical professional. If cancer is suspected, a biopsy of the area is taken and evaluated under a microscope to determine if the cells are cancerous. This testing will also establish what type of cancer is present.^[1]

In the case of melanoma, further clinical examination of the cancer site is likely to be performed to look for signs of spreading throughout the body, known as metastasis. If such signs are found, tests will be performed to determine if and where the cancer has spread.^[2]

The primary treatment for skin cancer is surgical, with the tumor cut from the skin or destroyed (e.g., using cold liquid nitrogen). Although surgery is often sufficient on its own, some cases (based on factors like severity, location, and resistance to surgery) may require further treatment. This can take the form of radiation, chemotherapy, immunotherapy, and photodynamic therapy.^[1][3]

Several studies have looked at the effect of niacinamide, a form of vitamin B3, on the risk of skin cancer among people with a history of NMSC or actinic keratoses (a precancerous patch of skin usually caused by excessive ultraviolet light exposure). These trials collectively suggest that niacinamide supplementation (usually around 500 mg taken twice a day) lowers the risk of NMSC (specifically BCC and SCC) in this population.^[4]

One clinical trial of people at risk of skin cancer found that oral retinol (a form of vitamin A) reduced the risk of SCC, with no effect on the risk of BCC.^[5] Meanwhile, several randomized controlled trials have failed to find any effect of beta-carotene (a retinol precursor) on the risk of NMSC.^[6]

Finally, one randomized controlled trial of people with a history of NMSC found that selenium supplementation (200 μg per day) increased the risk of SCC skin cancer.^[7] This outcome was not seen in people with lower selenium levels (≤105 ng/mL), suggesting the effect of selenium may depend on meeting a certain threshold.

Drinking more coffee is associated with a lower risk of both BCC^[8] and melanoma, with these findings specific to caffeinated coffee.^[9]

A few prospective cohort studies have found that eating more citrus fruit (e.g., grapefruit, oranges) is associated with a higher risk of melanoma.^[10] This could be due to citrus containing psoralens, compounds that become carcinogenic when exposed to ultraviolet light.^[11]

Higher alcohol consumption is associated with a higher risk of BCC,^[12] SCC,^[12] and melanoma.^[13]

A higher intake of retinol (a form of vitamin A) is associated with a lower risk of melanoma,^[14] although high-quality research on the topic is somewhat limited.

Acetretin, a synthetic retinoid used for psoriasis, is sometimes given orally to reduce the risk of skin cancer.^[15] Due to the risk of severe side effects it carries, acitretin is only given to people at a sufficiently high risk of skin cancer (e.g., immunocompromised transplant recipients).

Exposure to ultraviolet (UV) light, most commonly from sunlight, is generally considered the modifiable risk factor attributable to the greatest number of skin cancers.^[16][17] In general, the risk of BCC and SCC increases with greater cumulative sun exposure, whereas the risk of melanoma increases with frequency of sunburns.^[18] Tanning beds are also a significant source of UV light and their use is associated with a higher risk of skin cancer, both NMSCs and melanoma.^[19][20][21]

Skin color has a strong relationship with skin cancer risk, since melanin absorbs UV rays, providing some degree of protection against its effects. As a result, the risk of melanoma is several times higher among light-skinned compared to dark-skinned people.^[22]

Several drugs and even food-derived compounds are classified as photosensitizing, meaning they increase the skin’s sensitivity to UV light and potentially increase the risk of skin cancer when combined with sunlight exposure.^[23] Examples of photosensitizing medications are tetracycline, doxycycline, quinolones, and thiazide diuretics.

Finally, because the immune system plays an important role in inhibiting skin cancer development, the use of a number of medications with immunosuppressive effects are associated with a higher risk of skin cancer. This includes TNF-a inhibitors,^[24] methotrexate,^[25][26] cyclosporin,^[27][28] and tacrolimus.^[29] As a result of this phenomenon, organ transplant recipients who require immune-supressing medications (to prevent organ rejection) are at a much higher risk of SCC than the general population.^[30]