Epidemiological Support for an Hypothesis for Melanoma Induction Indicating a Role for UVA Radiation

Abstract

An hypothesis for melanoma induction is presented: UV radiation absorbed by melanin in melanocytes generates products that may activate the carcinogenic process. Products formed by UV absorption in the upper layers of the epidermis cannot diffuse down as far as to the melanocytes. Thus, melanin in the upper layer of the skin may be protective, while that in melanocytes may be photocarcinogenic. Observations that support this hypothesis include: (1) Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (2) Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians. (3) Among sun-sensitive, poorly tanning persons, frequent UV exposures are associated with increased risk of melanoma, whereas among sun-resistant, well-tanning persons, increased frequency of exposure is associated with decreased melanoma risk. (4) It is likely that UVA, being absorbed by melanin, might have a melanoma-inducing effect. This is in agreement with some epidemiological investigations which indicate that sun-screen lotions may not protect sufficiently against melanoma induction. The relative latitude gradient for UVA is much smaller than that for UVB. The same is true for the relative latitude gradient of cutaneous malignant melanoma as compared with squamous cell carcinoma and basal cell carcinoma. Under the assumption that the average slopes of the curves relating incidence rates with fluences of carcinogenic UV radiation are similar for melanomas and nonmelanomas, these facts are in agreement with the assumption that UVA plays a significant role in the induction of melanomas in humans. This is in agreement with the experimental results with Xiphophorus.

Malignant melanomas on head/neck and foot: differences in time and latitudinal trends in Norway

“…It is commonly believed that UVB, and possibly UVA, from solar radiation are the main melanomagenic agents for humans. 7,[9][10][11] Possible mechanisms for CMM carcinogenesis have been reviewed by several authors. 1,12,13 Increasing trends of CMM rates have been observed for a long time and are generally explained by increased sun exposure, notably in vacations and holidays (intermittent exposures).…”

The Monodelphis Melanoma Model: Initial Report on Large Ultraviolet A Exposures of Suckling Young

“…In this species, melanoma induction occurs not only at the UVB narrow-range wavelengths (302 and 313 nm) but also into UVA (365 nm) and to visible light (405 and 436 nm) (1-3), suggesting that wavelengths not absorbed directly in DNA are effective in induction. Epidemiological support for this suggestion has been summarized by Moan et al (4). A South American opossum, Monodelphis domestica, provides a useful opportunity to compare the effectiveness of known doses of UVB and UVA as inducers of melanoma in a mammal.…”

Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis

“…Adverse effects in the skin following exposure to UV radiation are widely recognized (1)(2)(3)(4)(5)(6)(7) and can result in photocarcinogenesis, particularly in fair/light skin. Whether the photoprotection afforded the skin by melanin is due solely to its role as a UV filter, or whether other properties of melanin or skin are also involved, is an important question (8 -10).…”