Evolved Adaptation to Low Ultraviolet Radiation May Be the Main Cause of Malignant Melanoma

Background: The High ultraviolet radiation (UVR), high malignant melanoma of skin (C43) theory has poorly explained the epidemiology of C43 regionally and globally. We hypothesize that generational evolution of low melanin production in response to low ultraviolet radiation (UVR) exposure in populations may be the principal determinant of C43 worldwide. Methods: Country-specific estimates of C43 incidence rate average daily UVR exposure, skin colour, socioeconomic status (GDP PPP), magnitude of reduced natural selection (Ibs), life expectancy e60 (ageing), urbanization and percentage of European diasporas/descendants were matched with C43 incidence rate. Findings: Nonparametric correlation (ρ) identified that C43 rate correlated inversely with UVR levels worldwide. This relationship remained significant when GDP PPP, Ibs, ageing and urbanization effects were kept constant in partial correlation. Post hoc Bonferroni revealed that, among WHO regions, the means of C43 incidence in Europe were significantly higher than in the other five regions, but the mean UVR in Europe was significantly lower than in any other region. Stepwise linear regression selected UVR as one of the variables which had the greatest influence on C43 in three sets of data. However, when both depigmentation and UVR were incorporated in the WHO Europe country grouping, UVR was removed as the variable with the greatest influence on C43. Interpretation: Our study, statistically suggests that melanoma occurrence is not attributable to UVR exposure. Low melanin production has adaptively evolved over generations of low UVR exposure and represents an ultimate risk factor for C43 as it involves changes of genetic traits. Funding Statement: Wood Jones Bequest to the University of Adelaide. Declaration of Interests: The authors have no competing interests to declare. Ethical Approval Statement: This study does not involve any human participants or animals. Ethical approval is not required.