Mr. Chips: <b>“Appears there are a number of studies, recent and old, that find direct relation between exposure and melanoma using direct studies on animals, not petri dishes of microorganisms as is the Ames test.”</b>
I've wasted more than two hours searching in PubMed (under “skin cancer UV” keywords as you suggested) for the “direct relation” between exposure and melanoma. The overwhelming majority of studies related to melanomas didn't mention UV, but genetic factors, chemical, etc. but I found this study that sheds some light onto the subject:<dir><b>Animal models of melanoma: an HGF/SF transgenic mouse model may facilitate experimental access to UV initiating events.</b>
Noonan FP, Dudek J, Merlino G, De Fabo EC.
Laboratory of Photobiology and Photoimmunology, Department of Environmental and Occupational Health, School of Public Health and Health Services, The George Washington University School of Medicine, Washington, DC, USA.
drmfpn@gwumc.edu
Cutaneous malignant melanoma, the most lethal of the skin cancers, known for its intractability to current therapies, continues to increase in incidence, providing a significant public health challenge. There is a consensus that skin cancer is initiated by sunlight exposure. For non-melanoma skin cancer there is substantial evidence that chronic exposure to the ultraviolet B radiation (UVB) (280-320 nm) portion of the sunlight spectrum is responsible. Experimentally, UVB is mutagenic and chronic UVB exposure can cause non-melanoma skin cancer in laboratory animals. Non-melanoma tumors in animals and in humans show characteristic UVB signature lesions in the tumor suppressor p53 and/or in the patched (PTCH) gene. An action spectrum or wavelength dependence for squamous cell carcinoma in the mouse shows a major peak of efficacy in the UVB. <b>For malignant melanoma, however, the situation is unclear and the critical direct target(s) of sunlight in initiating melanoma and even the wavelengths responsible are as yet unidentified.</b> This lack of information is in major part a result of a paucity of animal models for melanoma which recapitulate the role of sunlight in initiating this disease. The epidemiology of melanoma differs significantly from non-melanoma skin cancer. Intense sporadic sunlight exposure in childhood, probably exacerbated by additional adult exposure, <b>is associated</b> with elevated melanoma risk. Melanoma is also a disease of <b>gene-environment interactions with underlying genetic factors playing a significant role.</b> These major differences indicate that <b>extrapolation from information for non-melanoma skin cancer to melanoma is unlikely to be useful.</b></dir>
Then, an example of studies found in PubMed:<dir>Toxicol Appl Pharmacol. 2004 Mar 15;195(3):298-308.
<b>Toxic effects of ultraviolet radiation on the skin.</b>
Matsumura Y, Ananthaswamy HN.
Department of Dermatology, Kansai Medical University, Osaka 570-8507, Japan.
matsumy@takii.kmu.ac.jp
Ultraviolet (UV) irradiation present in sunlight is an environmental human carcinogen. The toxic effects of UV from natural sunlight and therapeutic artificial lamps are a major concern for human health. The major acute effects of UV irradiation on normal human skin comprise sunburn inflammation (erythema), tanning, and local or systemic immunosuppression. At the molecular level, UV irradiation causes DNA damage such as cyclobutane pyrimidine dimers and (6-4) photoproducts, which are usually repaired by nucleotide excision repair (NER). Chronic exposure to UV irradiation leads to photoaging, immunosuppression, and ultimately photocarcinogenesis. Photocarcinogenesis involves the accumulation of genetic changes, as well as immune system modulation, and ultimately leads to the development of skin cancers. In the clinic, artificial lamps emitting UVB (280-320 nm) and UVA (320-400 nm) radiation in combination with chemical drugs are used in the therapy of many skin diseases including psoriasis and vitiligo. Although such therapy is beneficial, it is accompanied with undesirable side effects. Thus, UV radiation is like two sides of the same coin--on one side, it has detrimental effects, and on the other side, it has beneficial effects.</dir>
Where you can see “melanoma” is not mentioned as a result of UV radiation exposure.
The next study (below) talked about melanoma and RR (risk ratios), but as you see there are too many uncertainties and no direct relationship. As this no epidemiological study, it has not too much validity because it has not “screened out” all factors that could induce melanomas. BTW, dermatologists don't have very clear what might induce melanomas. They keep searching, but no definitive study has yet established a recognized factor. What puzzle researchers is that melanoma frequently occur in places that have ever been exposed to any kind of radiation (UV, or X-rays, or whatever), as in the soles of our feet, inside the mouth, armpits, or buttocks.<dir><b>Cutaneous melanoma: hints from occupational risks by anatomic site in Swedish men.</b>
Perez-Gomez B, Pollan M, Gustavsson P, Plato N, Aragones N, Lopez-Abente G.
Cancer and Environmental Epidemiology Area, National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain.
bperez@isciii.es
AIMS: To improve knowledge of the epidemiology of melanoma by comparing occupational risks of cutaneous melanoma (CM) by anatomic site in Swedish workers. … For each location, occupational risk ratios (RRs) were extracted from Poisson regression models adjusted by age, period, town size, and geographical area. … Risk patterns for different locations were compared. <b>RESULTS:</b> High RRs for different sites were found among workers exposed to UV sources (dentists, physiotherapists, and lithographers), and sun exposed workers (harbour masters, and lighthouse/related work). Risk excesses were seen in fur tailors, tanners/fur dressers, patternmakers/cutters, electrical fitters/wiremen, telephone/telegraph installers/repairmen, and some glass/pottery/tile workers. Results for lower and upper limbs were significantly correlated but somewhat independent of those <b>found in thorax, the most frequent location</b> … Specific risk excesses were found for rolling mill workers in head/neck, for chimney sweeps in upper limbs, and <b>for aircraft pilots/navigators/flight engineers in lower limbs.
CONCLUSIONS:</b> High RRs in the trunk among occupations with UV exposure from <b>artificial sources <font color=#ff0000>suggest</font> an effect not restricted to exposed sites</b>. An unusual distribution of cases and RRs in chimney sweeps, rolling-mill, or glass/pottery/tile workers <font color=#ff0000><b>suggests</b></font> local effects of exposures.</dir>
To "suggest" is prove of nothing. To "associate" is to prove nothing.
And then there is this strange study that goes “against the grain”: it finds UV is beneficial!
<b>A moderately low phosphate intake may provide health benefits analogous to those conferred by UV light - a further advantage of vegan diets.</b>
McCarty MF.
Pantox Laboratories, San Diego, CA 92109, USA.
mccarty@pantox.com
Although exposure to ultraviolet light is often viewed as pathogenic owing to its role in the genesis of skin cancer and skin aging, there is growing epidemiological evidence that such exposure may decrease risk for a number of more serious cancers, may have a favorable impact on blood pressure and vascular health, and may help to prevent certain autoimmune disorders - in addition to its well-known influence on bone density. Most likely, these health benefits are reflective of improved vitamin D status. Increased synthesis or intake of vitamin D can be expected to down-regulate parathyroid hormone (PTH), and to increase autocrine synthesis of its active metabolite calcitriol in certain tissues; these effects, in turn, may impact cancer risk, vascular health, immune regulation, and bone density through a variety of mechanisms. Presumably, a truly adequate supplemental intake of vitamin D - manyfold higher than the grossly inadequate current RDA - could replicate the benefits of optimal UV exposure, without however damaging the skin.</dir
<b>Conclusion:
There is no consensus at all over the genesis of melanoma.</b> Some people try to link melanomas with UV, some others say there is no evidence for that claim. We'll have to wait until definitive solid evidence proves that UV radiation is to blame for melanoma – or not.
Now you make some research and find those studies that prove without doubt that UV radiation is DIRECTLY RESPONSIBLE for melanomas. Do your homework!