Epidemiological support for an hypothesis for melanoma induction indicating a role for UVA radiation

An hypothesis for melanoma induction is presented: UV radiation absorbed by melanin in melanocytes generates products that may activate the carcinogen ic process. Products formed by UV absorption in the upper layers of the epi dermis cannot diffuse down as far as to the melanocytes. Thus, melanin in t he upper layer of the skin may be protective, while that in melanocytes may be photocarcinogenic. Observations that support this hypothesis include: ( I) 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 larg er than the corresponding ratio for Caucasians, (2) Albino Africans, as com pared with normally pigmented Africans, seem to have a relatively small ris k of getting cutaneous malignant melanomas compared to nonmelanomas. This i s probably also true for albino and normally pigmented Caucasians. (3) Amon g sun-sensitive, poorly tanning persons, frequent UV exposures are associat ed with increased risk of melanoma, wherease among sun-resistant, well-tann ing persons, increased frequency of exposure is associated with decreased m elanoma risk. (4) It is likely that WA, being absorbed by melanin, might ha ve a melanoma-inducing effect. This is in agreement with some epidemiologic al investigations which indicate that sun-screen lotions may not protect su fficiently against melanoma induction. The relative latitude gradient for W A is much smaller than that for UVB. The same is true for the relative lati tude gradient of cutaneous malignant melanoma as compared with squamous cel l carcinoma and basal cell carcinoma. Under the assumption that the average slopes of the curves relating incidence rates with fluences of carcinogeni c UV radiation are similar for melanomas and nonmelanomas, these facts are in agreement with the assumption that UVA plays a significant role in the i nduction of melanomas in humans. This is in agreement with the experimental results with Xiphophorus.