MelanomaExposure to sunlight

Primary risk factors for melanoma may be high exposure to UVA without much UVB1 2 3 4 5 and high doses of UVB, leading to sunburn6. At all ages sunburns seem to be an important risk factor for melanoma7.

The role of ultraviolet (UV) exposure in melanoma genesis is often misunderstood. The two most important mechanisms by which UV exposure increases the risk of melanoma are induction of DNA damage, often after sunburning, primarily due to wavelengths from 290 to 325 nm (the erythema region) and oxidative damage caused by free radicals generated during UVA exposure.

Both mechanisms can act on melanocytes as well as on immune cells in the skin and in that way decrease the efficiency of immuno-effects on premalignant melanocytes.

Wearing sunscreen, which blocks erythemal radiation well, but UVA less well, will influence the melanoma risk associated with UV exposure. Sunscreen use seems to reduce the risk of melanoma for latitudes below about 40 degrees (near the latitude for Manhattan and Salt Lake City) but to increase the risk at higher latitudes6

In addition to vitamin D production, chronic UV exposure also causes elastosis (breakdown of elastic tissue or collagen). For reasons not fully understood, melanomas develop less well in skin with elastosis. For example, melanoma in Sweden develops on the face and hands from around the age of 55 years, but from around the age of 35 years on the trunk and legs8. The difference seems to be due to whether the skin is chronically exposed as from occupation or sporadically exposed as from trips to the beach. Smoking also causes elastosis or skin wrinkling, and smokers have reduced risk of melanoma9 10. Further discussion on the role of sun exposure on different body sites is given by Caini11.

A study in Connecticut found increased survival for persons with evidence of large sun exposure:

Sunburn, high intermittent sun exposure, and solar elastosis were statistically significantly inversely associated with death from melanoma. Melanoma thickness, mitoses, ulceration, and anatomic location on the head and neck were statistically significantly positively associated with melanoma death. In a multivariable competing risk analysis, skin awareness (with versus without, HR = 0.5, 95% CI = 0.3 to 0.9, P = .022) and solar elastosis (present versus absent, HR = 0.4, 95% CI = 0.2 to 0.8, P = .009) were strongly and independently associated with melanoma death after adjusting for Breslow thickness, mitotic index, and head and neck location, which were also independently associated with death12.

A group in Italy has conducted a number of meta-analyses of risk factors for melanoma. Meta-analyses are quantitative reviews of studies on a particular topic. Among the findings were:

  • A high number of nevi (moles) is a significant risk factor13
  • Intermittent sun exposure and sunburn history were shown to play considerable roles as risk factors for melanoma, whereas a high occupational sun exposure seemed to be inversely associated to melanoma14
  • Phenotypic factors such as pale skin, freckles, blue eye color, and red or blond hair color are associated with increased risk of melanoma15
  • The melanocortin-1-receptor (MC1R), one of the major genes that determine skin pigmentation, has many variants. Those associated with red hair and fair skin were significantly correlated with melanoma risk in a manner suggesting a role in melanoma development via pigmentary and non-pigmentary pathways16

A study in Germany found that outdoor activities in childhood were protective against melanoma, although sunburn in childhood was a risk factor17. A study of cancer mortality rates in Spain using mortality rates for nonmelanoma skin cancer as an index of solar UVB exposure, found melanoma mortality rate inversely correlated with this index for females but uncorrelated for males18. Those who have signs of chronic sun exposure, such as farmers and other outdoor workers, are not very likely to get melanoma in general19.

A case-control study in England found “Overall the clearest relationship between reported sun exposure and risk was for average weekend sun exposure in warmer months, which was protective (OR 0.67, 95% CI 0.50-0.89 for highest versus lowest tertile of exposure)”20.

A study from Australia, which has the fairest-skinned people living in region of very high solar UV doses found in general there was little significant correlation between amount of sun exposure and risk of melanoma. However, rates were increased by a factor of two-t0-three for those diagnosed with melanoma prior to age 29 years who had more than 10,000 hours of sun exposure21. As the average mortality rate for melanoma is 1 per 100,000 inhabitants per year aged 23-33 years [WHO mortality database], implying an incidence rate of 5-10 per 100,000 inhabitants per year, this does not imply a large absolute risk. Breast cancer mortality rates for women of that age range are somewhat higher.

There is evidence from ecological studies that UVA is a risk factor for melanoma. For those with northern European ancestry, melanoma rates decrease with increasing latitude with a gradient that is much lower than for either squamous cell carcinoma or basal cell carcinoma4 5. UVB is an important risk factor for the two non-melanoma skin cancers, and UVB doses change more with latitude than do UVA doses.

There is also laboratory evidence that both UVA and UVB are involved in the etiology of melanoma based on molecular markers of photodamage22 23

Uveal and vulvar melanoma are also vitamin D sensitive24. Under conditions of increasing rates of melanoma on exposed skin, related to latitude or to time, the rates of vulval and uveal melanomas decrease.

Darker skin pigmentation from higher concentration of eumelanin reduces the risk of melanoma by reducing the penetration of UV in the skin as well as repairing the chromosomal damage by UV25 26.

People are often advised to avoid the sun or to use sunscreens when in the sun. This advice does not necessarily lead to reduced risk of melanoma6, while it certainly reduces production of vitamin D.

It was estimated that if all Americans raised their serum 25(OH)D levels to over 40 ng/mL from 16 ng/mL for Black Americans, 21 ng/mL for Hispanic Americans, and 26 ng/mL for White Americans27, mortality rates might be reduced by 400,000 deaths/year while melanoma death rates might rise from 9000/year to 18,00028.

Page last edited: 18 July 2011


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