Women with fair phenotypes seem to confer a survival advantage in a low UV milieu. A nested matched case control study

Abstract

Background Sun exposure in combination with skin pigmentation is the main determinant for vitamin D status. Human skin color seems to be adapted and optimized for regional sun ultraviolet (UV) intensity. However, we do not know if fair, UV-sensitive skin is a survival advantage in regions with low UV radiation. Methods A population-based nested case-control study of 29,518 Caucasian women, ages 25 to 64 years from Southern Sweden who responded to a questionnaire regarding risk-factors for malignant melanoma in 1990 and followed for 25 years. For each fair woman, defined as having red hair or freckles (n = 11,993), a control was randomly selected from all non-fair women from within the cohort of similar age, smoking habits, education, marital status, income, and comorbidity, i.e., 11,993 pairs. The main outcome was the difference in allcause mortality between fair and non-fair women in a low UV milieu, defined as living in Sweden and having low-to-moderate sun exposure habits. Secondary outcomes were mortality by sun exposure, and among those non-overweight. Results In a low UV milieu, fair women were at a significantly lower all-cause mortality risk as compared to non-fair women (log rank test p = 0.04) with an 8% lower all-cause mortality rate (hazard ratio [HR] = 0.92, 95% CI 0.84-1.0), including a 59% greater risk of dying from skin cancer among fair women (HR 1.59, 95% CI 1.26-2.0). Thus, it seem that the beneficial health effect from low skin coloration outweigh the risk of skin cancer at high latitudes.

The evolution of human skin pigmentation involved the interactions of genetic, environmental, and cultural variables

“…Vitamin D is produced in the upper epidermis through UVB‐induced catalysis of 7‐DHC into pre‐D, and it is required in the dermis to preserve NO production required for healthy vasodilation. This important function of vitamin D probably accounts for the intriguing finding of reduced all‐cause mortality in a large cohort of lightly pigmented Scandinavian women reported by Lindqvist and colleagues (Lindqvist et al., 2020 ). The role of vitamin D’s role in eNOS signaling, control of vasodilation, and regulation of blood pressure warrants further investigation in an evolutionary context with respect to the evolution of skin pigmentation under low UVR conditions (Wolf et al., 2020 ).…”

Increased 25(OH)D3 level in redheaded people: Could redheadedness be an adaptation to temperate climate?

“…This conclusion finds further support in the results of a recent case‐control study performed on a sample of 24,000 Swedish women, which showed that women with red hair or freckles have a survival advantage in low UV environment. [ 33 ] It is possible that the positive effects of redheadedness prevail over this trait's negative effects only in high latitudes, for instance in Sweden and Scotland, countries situated largely north of the 55° parallel, [ 34 ] while in other parts of the world, they are sustained by gene flow [ 35 ] and/or sexual selection. [ 10,11 ]…”

“…This conclusion finds further support in the results of a recent case-control study performed on a sample of 24,000 Swedish women, which showed that women with red hair or freckles have a survival advantage in low UV environment. [33] It is possible that the positive effects of redheadedness prevail over this trait's negative effects only in high latitudes, for instance in Sweden and Scotland, countries situated largely north of the 55° parallel, [34] while in other parts of the world, they are sustained by gene flow [35] and/or sexual selection. [10,11] The currently most popular hypothesis regarding the persistence of redheadedness and fair skin suggests that the decrease of eumelanin concentration in fair-skinned subjects and decrease of the eumelanin-pheomelanin ratio in redheaded individuals (who are mostly but not always fair-skinned) are an adaptation for synthesis of sufficient amount of provitamin D in regions with low, seasonally fluctuating intensity of UVB radiation.…”

Higher ultraviolet light exposure is associated with lower mortality: an analysis of data from the UK Biobank cohort study

“…In a case-control study of Swedish women with low-to-moderate sun exposure habits, women with fair phenotypes (the most UV-sensitive) had an 8% lower all-cause mortality rate than non-fair women, despite having a greater risk of dying from skin cancer. [5] Several biologically plausible mechanisms exist for a relationship between ultraviolet A (UVA) and ultraviolet B (UVB) exposure and positive health outcomes. UVB synthesises vitamin D in exposed skin.…”