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

Abstract Objective:The low melanin production (depigmentation) evolved from low ultraviolet radiation may be the principal determinant of malignant melanoma of skin (C43).Design:Country-specific estimates of C43 incidence, daily UVR exposure, skin colour (EEL), socioeconomic status (GDP PPP), magnitude of reduced natural selection (I bs ), ageing, urbanization, percentage of European descendants (Eu%), and depigmentation measured by blonde hair colour, were subjected to statistical analyses. Data were derived from WHO, United Nations, World Bank databases and the literature.Setting:Ecological analysisParticipants:182 individual countries.Main outcome measures:Parametric and non-parametric correlations, partial correlation analyses keeping confounders statistically constant, multivariate regressions and analyses of variance.Results:Worldwide, UVR exposure was in negative correlation with C43 (“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, I bs , ageing and urbanization were statistically kept constant.In stepwise linear regression analysis, UVR was the variable having greatest negative influence on C43 incidence (R 2 =0.301).Worldwide, C43 incidence was in strong correlation with Eu% (r = 0.711, p<0.001). The inverse relationships between C43 and UVR exposure (r = -0.498, r<0.001) and Eu% (r = 0.477, p<0.001) remained significant in partial correlation analysis.When C43 incidence rate was standardized 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 C43 incidence (r = 0.705, p<0.001, n= 48). Partial correlation analysis revealed that C43 correlated to depigmentation significantly (r=0.315, p<0.01). However, UVR showed almost nil correlation with C43 when depigmentation, together with the other four potential confounders was included as the controlled variable.Conclusions:  C43 incidence may not be attributable to UVR exposure. Low melanin production, genetically determined, that has adaptively evolved over generations represents an ultimate risk factor for C43.