Ultraviolet radiation is the dominant cause of melanoma, responsible for 83% of all new cases worldwide in 2022 according to the International Agency for Research on Cancer. But UV exposure isn’t the whole story. Genetics, immune function, and even physical trauma can play a role, and some melanomas develop in places the sun never reaches.
How UV Radiation Damages Skin Cells
Melanoma begins in melanocytes, the cells that produce the pigment giving your skin its color. When UV radiation hits these cells, it damages their DNA in ways that can eventually trigger uncontrolled growth. The two types of UV radiation do this through different mechanisms.
UVB rays penetrate only the outer layer of skin (the epidermis) and cause direct DNA damage. They physically distort the structure of DNA, creating defective links between neighboring molecules. About 80% of these defects are a type called cyclobutane pyrimidine dimers. When the cell’s repair machinery fails to fix them, they produce characteristic mutations, essentially rewriting the genetic code in a way that can push the cell toward cancer.
UVA rays penetrate deeper, reaching the dermis, and work more indirectly. They generate reactive oxygen species, unstable molecules that attack DNA through oxidative stress. UVA also suppresses the skin’s local immune defenses three times more than UVB does during typical daily sun exposure. This matters because your immune system normally helps detect and destroy cells with dangerous mutations before they can grow into tumors.
One of the more surprising discoveries in recent years is that UV damage doesn’t stop when you go indoors. Researchers found that melanocytes continue generating DNA defects for hours after UV exposure ends, through a process involving melanin itself. These “dark” DNA lesions form in complete absence of sunlight and cause the same types of mutations seen from direct UV exposure. Ironically, the pigment that protects other skin cells appears to contribute to ongoing damage within melanocytes.
Why Childhood Sunburns Matter So Much
Not all UV exposure carries equal risk. Intense, intermittent burns, especially in childhood, appear far more dangerous than steady, moderate sun exposure over time. A Mendelian randomization study estimated that childhood sunburn increases melanoma risk roughly fivefold. This outsized effect likely reflects the vulnerability of developing skin: children’s melanocytes are dividing rapidly, and DNA damage during this period has more opportunities to become permanently embedded in the cell lineage.
Indoor tanning carries similar risks. A large meta-analysis found that people who first used tanning beds at a young age had a 47% higher risk of developing melanoma compared to those who never used them. Tanning beds emit primarily UVA radiation, which for years was considered the “safer” type. That assumption has not held up.
Where UV Exposure Is Highest
Geography plays an obvious role. In Australia, New Zealand, northern Europe, and North America, more than 95% of melanoma cases are attributable to UV radiation. The proportion is slightly lower in equatorial regions with predominantly darker-skinned populations, but the global average still sits at 83%. Men face a somewhat higher UV-attributable fraction (86%) than women (79%), likely reflecting differences in occupational and recreational sun exposure patterns.
Genetic Mutations That Drive Melanoma
Almost 80% of sporadic melanomas carry a mutation in one of two genes: BRAF or NRAS. These genes control a signaling pathway that tells cells when to grow and divide. When either is mutated, the growth signal gets stuck in the “on” position, driving uncontrolled cell division. BRAF mutations are the more common of the two and are the target of several modern melanoma therapies.
Some people inherit genetic changes that make them more vulnerable from the start. Mutations in a gene called CDKN2A, which normally acts as a brake on cell growth, run in families with high rates of melanoma. In one study of Swedish families carrying CDKN2A mutations, 95% of their melanomas had additional NRAS mutations, compared to much lower rates in non-hereditary cases. This suggests that inherited genetic vulnerability and UV-driven mutations can compound each other.
Skin Type and Pigmentation
Lighter skin carries substantially higher melanoma risk. People who always burn and never tan have the least natural protection, while those with very dark skin have a much-reduced risk. But this relationship isn’t as simple as a sliding scale. The Fitzpatrick skin type system, which classifies skin from type I (always burns) to type VI (never burns), was designed to predict tanning response rather than cancer risk. Its categories don’t map neatly onto actual melanoma incidence, and people with darker skin can and do develop melanoma, often with delayed diagnosis.
Data on melanoma in people of color remains severely limited. Skin cancer registries are nearly nonexistent in many less-developed countries, and clinical research has historically underrepresented darker-skinned populations. This gap is particularly dangerous because melanoma in darker skin tends to appear in locations that aren’t associated with sun exposure, making it easier to miss.
Melanoma Without Sun Exposure
Some melanomas arise in places that rarely or never see sunlight: the palms, soles of the feet, and beneath fingernails or toenails. This subtype, called acral lentiginous melanoma, doesn’t carry the UV-signature mutations found in other melanomas. Its causes remain less well understood, but mechanical stress appears to play a role. Incidence is higher in weight-bearing areas of the foot like the heel and forefoot, and melanoma in the arch of the foot occurs more often in obese patients. There is also some correlation with prior penetrative injuries to the skin.
Acral lentiginous melanoma accounts for a small fraction of melanoma overall, but it represents a much larger share of melanoma cases in people with darker skin, precisely because UV-driven melanoma is rarer in this group. It’s a reminder that melanoma is not a single disease with a single cause.
Atypical Moles and Melanoma Risk
Atypical moles, sometimes called dysplastic nevi, are larger than ordinary moles (typically more than 5 millimeters across), with irregular borders, uneven color ranging from pink to dark brown, and a flat or slightly pebbly surface. Having them doesn’t mean you’ll get melanoma. Only rarely does an individual atypical mole transform into cancer. But the number of atypical moles you have serves as a marker of your overall risk: someone with more than five atypical moles has roughly 10 times the melanoma risk of someone with none.
How the Immune System Keeps Melanoma in Check
Your immune system plays a critical role in controlling melanocytes that have acquired dangerous mutations. The clearest evidence comes from organ transplant recipients, who take medications to suppress their immune systems and prevent organ rejection. Their melanoma risk is two to five times higher than the general population’s, and their melanoma-specific mortality is roughly three times higher.
The pattern of increased risk among transplant recipients reveals something important about how immunity and melanoma interact. Localized, thin tumors (less than 1 millimeter thick) were more common in patients taking certain immunosuppressive drugs that also make skin more sensitive to UV damage. Meanwhile, more advanced tumors peaked within four years of transplantation and were associated with treatments that broadly deplete the immune cells responsible for identifying and destroying abnormal cells. This suggests that a healthy immune system normally catches and eliminates many early melanomas before they ever become detectable.
What About Air Pollution?
Air pollutants like fine particulate matter and polycyclic aromatic hydrocarbons are known carcinogens for several cancer types, which has raised questions about a potential link to melanoma. However, a recent genetic analysis found no evidence supporting a causal association between common air pollutants (including PM2.5, PM10, and nitrogen oxides) and melanoma risk in European populations. UV radiation remains overwhelmingly the primary environmental driver.