Skin cancer is caused primarily by ultraviolet (UV) radiation damaging the DNA inside skin cells, triggering mutations that lead to uncontrolled growth. But UV exposure isn’t the whole story. Genetics, immune system function, chemical exposures, and even certain viruses all play a role in determining who develops skin cancer and which type they get.
How UV Radiation Damages Skin Cells
Sunlight contains two types of UV radiation that reach your skin: UVB, which causes sunburns, and UVA, which penetrates deeper. Both wavelengths damage DNA in two ways. They can be absorbed directly by DNA, creating structural defects called pyrimidine dimers that distort the genetic code. They also trigger the production of reactive oxygen species, unstable molecules that attack DNA indirectly. Every time your skin cells divide with this damaged DNA, there’s a chance the repair machinery will miss something, locking in a permanent mutation.
These mutations accumulate over a lifetime. When they hit the genes that control cell growth, a single skin cell can start dividing without the normal brakes. That’s the beginning of a tumor.
Different Exposure Patterns Cause Different Cancers
Not all sun exposure carries the same risk for every type of skin cancer. Squamous cell carcinoma is closely tied to cumulative, long-term sun exposure. People with chronic occupational exposure in the decade before diagnosis face significantly elevated risk. Severe sunburns also matter: experiencing very severe burns once or more per year in the ten years before diagnosis is associated with a tenfold increase in squamous cell carcinoma risk.
Melanoma, the most dangerous form, follows a different pattern. It’s more strongly linked to intense, intermittent sunburns, particularly during youth. A large study tracking over 108,000 women for roughly 20 years found that those who experienced five or more blistering sunburns between ages 15 and 20 had an 80 percent increased risk of melanoma. The same group also had a 68 percent increased risk of basal cell and squamous cell carcinomas. Childhood and adolescent skin appears especially vulnerable because rapidly dividing cells are more likely to lock in UV-induced mutations permanently.
Basal cell carcinoma, the most common skin cancer, falls somewhere in between. Both cumulative exposure and intermittent burning contribute, though it tends to appear on sun-exposed areas like the face and neck.
Genetic Factors That Raise Your Risk
Your genes influence how well your skin defends itself against UV damage, and some people start at a significant disadvantage. One of the most studied genetic factors involves variants of a gene called MC1R, which controls the type of pigment your skin produces. When MC1R functions normally, it signals skin cells to produce eumelanin, the dark pigment that absorbs UV radiation and shields DNA. When variants reduce or eliminate the receptor’s function, skin cells instead produce pheomelanin, a reddish-yellow pigment common in people with fair skin and red hair.
Pheomelanin doesn’t just fail to protect against UV. It actively generates free radicals when exposed to sunlight, adding another source of DNA damage on top of the UV radiation itself. Research in the Journal of Investigative Dermatology found that the increased melanoma risk from MC1R variants is largely independent of skin type and hair color, meaning even people who don’t look stereotypically fair-skinned can carry these higher-risk gene variants.
Mutations That Drive Melanoma Growth
Once UV damage starts accumulating, specific gene mutations act as the engine of cancer development. In melanoma, two mutations dominate: BRAF and NRAS. These genes sit along the same signaling pathway that tells cells when to grow and divide. When either one mutates, that growth signal gets stuck in the “on” position permanently. About 89 percent of melanoma patients carry a mutation in one of these two genes, and the mutations appear early, during the initial sideways-spreading phase of the tumor, before it grows deeper into the skin. Once present, these mutations persist through every stage of progression, including metastasis.
BRAF and NRAS mutations are mutually exclusive. A tumor will have one or the other, never both. This matters for treatment, since targeted therapies exist for BRAF-mutated melanomas.
Weakened Immune Systems and Skin Cancer
Your immune system constantly patrols for abnormal cells and destroys them before they can form tumors. When that surveillance breaks down, skin cancer risk climbs sharply. The clearest evidence comes from organ transplant recipients, who take medications to suppress their immune systems and prevent organ rejection.
A Canadian study of over 10,000 transplant recipients found that nearly 17 percent developed a skin cancer (basal cell or squamous cell carcinoma) after transplant, with a median time to diagnosis of about four years. Their overall skin cancer rate was nearly seven times higher than the general population. Squamous cell carcinoma, which is normally less common than basal cell carcinoma, becomes the dominant type in transplant patients, and these tumors tend to be more aggressive.
Other conditions that suppress the immune system, including HIV and certain blood cancers, carry similar increases in skin cancer risk, though the magnitude varies.
The Role of Viruses
Certain strains of human papillomavirus (HPV) have been linked to squamous cell carcinoma of the skin, particularly in people with compromised immune systems. The connection works differently than HPV’s well-known role in cervical cancer. In skin cancers, a group of HPV strains called beta-HPV types appear to act early in the process, amplifying the DNA-damaging effects of UV radiation. Once the cancer is established, the virus may no longer need to be active, a concept researchers call the “hit-and-run” hypothesis.
HPV proteins interfere with two of the cell’s most important tumor suppressors, p53 and retinoblastoma protein. These proteins normally halt cell division when DNA damage is detected. By disabling them, HPV allows damaged cells to keep dividing instead of stopping for repair or self-destructing. The VIRUSCAN study, which tested immunocompetent patients for dozens of HPV types, found an increased squamous cell carcinoma risk specifically associated with beta-HPV strains.
Chemical and Environmental Exposures
Arsenic is the best-established chemical cause of skin cancer. It occurs naturally in groundwater in many parts of the world and can also enter the environment through mining, metal smelting, and agricultural processes. People are exposed primarily through contaminated drinking water, food grown with contaminated irrigation water, and tobacco smoke.
Prolonged ingestion of arsenic-containing water is associated with increased risk of both skin cancer and bladder cancer. Arsenic-related skin cancers often appear as multiple lesions across the body, including areas not exposed to sunlight, which distinguishes them from UV-driven cancers. Historical medical treatments containing arsenic have also been clearly linked to skin cancer in studies tracking patients over decades.
Tanning Beds Carry the Same Risks
Indoor tanning devices emit the same UVA and UVB wavelengths as sunlight, and in concentrated doses. They cause the same types of DNA damage: direct pyrimidine dimers and indirect oxidative damage from reactive oxygen species. The World Health Organization classifies tanning beds as a Group 1 carcinogen, the same category as tobacco and asbestos. Using them before age 35 increases melanoma risk substantially, mirroring the vulnerability of younger skin to blistering sunburns from natural sunlight.
Risk Factors You Can’t Change
Several fixed characteristics raise your baseline risk. Fair skin that burns easily provides less natural UV protection. A large number of moles, particularly atypical or irregularly shaped ones, signals a higher melanoma risk. A family history of melanoma roughly doubles your own risk, reflecting shared genetic variants like MC1R and others that affect DNA repair. A personal history of any skin cancer significantly increases the chance of developing another one, since the underlying DNA damage and genetic susceptibility remain.
Age also plays a role, simply because mutations accumulate over time. Most non-melanoma skin cancers appear after age 50, though melanoma can strike younger adults, especially those with intense sun exposure histories or strong genetic risk factors.