Malignant melanoma more than just a sunburn story? By Dr Chris Barnes, Bangor Scientific and Educational Consultants October 2013. E-mail email@example.com Reference list updated March 2015
The main types of skin cancer are briefly reviewed and possible reasons for their increasing prevalence are raised. A hypothesis is raised that UV causes malignant melanoma excess risk when there is both vitamin D deficiency and increased radon gas levels. Further, public domain mapping for radon gas in the UK is used to explore the additional hypothesis that vitamin D might offer protection and further that there is an association of radon levels not only with squamous cell disease but also with malignant melanoma. The hypothesis is convincingly validated. In common with many cancers malignant melanoma cells exhibit increased oxidative stress, Sander et al 2003. Both UV radiation and nuclear radiation (from Radon) could be expected to mediate free radical reactions. Vitamin D has antioxidant properties which will tend to counter reactive oxygen species and products. Relevance for biology, epidemiology and sunscreen manufacturers is also discussed. Probably all cancers have co-initiators and co-promoters epidemiologists must start to understand this and must understand that Bayesian approaches, even simple, such as here are going to be the most productive route to outing the truth in this fascinating and complex realm.
Skin cancer falls into three main categories namely; basal cell carcinoma, squamous cell carcinoma and malignant melanoma. The first two have been associated with high doses of UVA and are the most common and least life threatening types but left untreated they can cause hideous disfigurement. Since sunbeds often have a huge imbalance in UVA to UVB and have up to double the total UV exposure of the sun they have been associated with an explosion of all types of skin cancer.
Increases in the more deadly malignant melanoma which involves the melanin producing cells or melanocytes were first reported in Europe in the 1940’s and continue to this day. Some have blamed the invention of the sunbed, see, for example, Westerdahl et al (1993) (1). Some have blamed the invention of the ‘foreign’ holiday. There are some very recent theories that all skin cancers may be caused by an imbalance in the natural ratios of UVA and UVB, see Maier et al (2001). To this end, the invention of sunscreen creams may have accentuated skin cancer and some cream’s contents may themselves be carcinogenic, Knowland et al 1993 and see (2). Supporting this is the notion that there is considerably more sunscreen use amongst young males in Australia than the USA, see Maclean and Gallagher 1998 (3) and yet Australia has considerably more Melanoma. Some have even shown an association with melanoma and the onset of Radio and TV broadcasting, see Hallberg and Johansson (2005) (4,), Hallberg 2007 (5) and Hallberg and Johansson (2011) (6). A limited study in Cornwall has shown an association of squamous cell cancer with household radon levels, see Wheeler et al 2012 (7).
Considering all types of skin cancer, isn’t it is ironic that UVB is essential for the body to manufacture vitamin D from sunlight. Of all the countries in Europe, Sweden is perhaps most badly affected by malignant melanoma. Sun deprived Swedes love travelling to warmer Mediterranean and Middle Eastern climes. One has to pose the question ‘is it their initial lack of vitamin D make them more susceptible to malignant melanoma?’
Very recently vitamin D has been branded by some a wonder vitamin with anti-cancer and immune boosting activity, see for example of several, Garland et al American Journal of Public Health 2006 (8). Skin cancers have also been associated with so called ROS (reactive oxygen species) and free radical reactions. UV can of course mediate such reactions as can nuclear radiation. There are emerging new theories as to how RFR (non-ionising radio frequency radiation) might even be able to do the same, see for an example of several, De Luliis et al (2009) (9) such findings which may indeed give more credulity to the work of Hallberg and Johannsson for example.
The purpose of this study is to use available public domain mapping for sunshine levels firstly to explore traditional association between UV and malignant melanoma excess risk and further together with use of mapping for vitamin D deficiency and mapping for radon to explore the additional hypothesis that vitamin D might offer protection and further that there may association of radon levels not only with squamous cell disease but also with malignant melanoma.
The results are obtained directly by visual inspection and human visual meta-analysis interpretation of the mapping data below.
UV and Malignant Melanoma Assumptions
Making the assumption that total UVA+UVB will be proportional to sunshine hours, it can very evidently be seen that there is clearly no simple association between this quantity and excess risk for the cancer. The latter which is just a high in the relatively un-sunny Scottish borders and North Lake District region as it is in the much sunnier Cornwall region. In the North West Scottish highlands which have least sunshine of all there is lower cancer risk but not the lowest. Clearly, then there are other factors at play.
Vitamin D protection
Some recent studies have suggested vitamin D might protect from other cancers, especially colorectal, see Gorham et al (2007) (10). No studies have suggested vitamin D could protect from malignant melanoma. Thus the findings presented here are entirely new.
Although not a perfect correlation, it can be seen that the regions of Britain which have populations with least vitamin D deficiency specifically in Spring seem to correspond with regions which have much lower malignant melanoma risk, except that is in the South West Midlands.
Radon another vital factor
Again not perfect but spatially very apparent and possibly significant is that regions of Britain which have high radon concentration s also seem to have excess risk for malignant melanoma.
Special cases which test and summarise the overall result and strongly support the hypothesis
Conclusions and Further Discussion
The complex hypothesis appears to have been validated.
Risk of malignant melanoma is minimised and indeed significantly lower than average by the protective action of vitamin D in Spring and Fall, irrespective of UV levels in Britain provided Radon exposure is also low.
When vitamin D deficiency extends all year and radon levels are high there is significant risk of malignant melanoma even for regions of Brittan which have low sunshine amounts and hence presumed lower UV exposure.
In common with many cancers malignant melanoma cells exhibit increased oxidative stress, see Sander et al 2003 (11). Both UV radiation and nuclear radiation (from Radon) could be expected to mediate free radical reactions. Vitamin D has antioxidant properties which will tend to counter reactive oxygen species and products.
Relevance for cancer biology
Associations have been shown in the past between Radon and non-melanoma cancers especially squamous cell types but it is believed this is the first study which shows an association with the more deadly melanoma type.
The protective effect of vitamin D is also very relevant for cancer biology in general.
It has certainly been shown that melanoma is simply not just a sunburn story.
Relevance for sunscreen technology
Sun screen creams, ironically, disturb the balance between UVA and UVB and UVB is essential for vitamin D formation in the skin. It is even possible that too much UVA without UVB might promote other problems.
Relevance for Epidemiology
Because probably all cancers have co-initiators and co-promoters epidemiologists must start to understand this and must understand that Bayesian approaches, even simple, such as the above are going to be the most productive route to outing the truth in this fascinating and complex realm.
Support for work of others in the field
This present work lend considerable independent support to the work Osborne (2002)  who stated that there is accumulating evidence that the vitamin D3/1,25(OH)2D3/VDR axis is important in malignant melanoma (MM) and importantly that MM cells express the VDR, and the antiproliferative and prodifferentiation effects of 1,25(OH)2D3 have been shown in cultured melanocytes, MM cells and MM xenografts. Further very importantly and totally consistent with the observations here with regard to Spring sunlight Osborne remarks that an inhibitory effect on the spread of MM cells has been demonstrated and that low serum levels of 1,25(OH)2D3 have been reported in MM patients and the VDR polymorphisms have been shown to be associated with both the occurrence and outcome of MM.
Indeed Osborne goes on to say that further work is necessary on the influence of serum vitamin D3 levels on the occurrence and prognosis of MM, the effects of sun protection measures on serum vitamin D3 levels in temperate climates and epidemiological studies on geographical factors and skin type on the prognosis of MM. In other words he points out the need for exactly the type of study I have done here.
Finally Osborne states it would seem mandatory to ensure an adequate vitamin D3 status if sun exposure were seriously curtailed, certainly in relation to carcinoma of breast, prostate and colon and probably also MM.