Evolved adaptation to low ultraviolet radiation may be the main cause of malignant melanoma independent of high ultraviolet radiation levels

Abstract Background: The low melanin production (depigmentation) evolved in response to low ultraviolet radiation may be the principal determinant of malignant melanoma of skin (C43). Methods: Worldwide country-specific estimates of melanoma incidence, daily UVR levels, skin colour (EEL), socioeconomic status (GDP PPP), magnitude of reduced natural selection (Ibs), ageing, urbanization, percentage of European descendants (Eu%), and depigmentation measured by blonde hair colour, were subjected to statistical analyses. Data for 182 individual countries were derived from WHO, United Nations, World Bank databases and the literature. Parametric and non-parametric correlations, partial correlation analyses keeping confounders statistically constant, multivariate regressions and analyses of variance were used. Results: Worldwide, UVR levels were in negative correlation with melanoma (C43) incidence (“rho” = -0.515, p<0.001). This relationship remained significant and negative in parametric partial correlation (r = -0.513, p<0.001) when GDP PPP, Ibs, ageing and urbanization were statistically kept constant. In stepwise linear regression analysis, UVR was the variable having greatest negative influence on melanoma incidence (R2=0.301). Melanoma incidence was in strong correlation with Eu% (r = 0.711, p<0.001). The negative relationship between melanoma and UVR levels (r = -0.498, r<0.001) and positive relationship of melanoma with Eu% (r = 0.477, p<0.001) remained significant in partial correlation analyses.When melanoma incidence rate was standardised on Eu% it did not correlate at all with UVR (“rho”=0.004, p=0.967, n=127). The country-specific depigmentation level strongly correlated with melanoma incidence (r = 0.705, p<0.001, n= 48) remaining significant in partial correlation (r=0.315, p<0.01). However, UVR showed nil no correlation with melanoma when depigmentation, together with the other four potential confounders was included as the controlled variable. Conclusions: Low melanin production, genetically determined, that has adaptively evolved over generations represents the principal risk factor for melanoma, while UVR has a secondary role.