25-Hydroxyvitamin D2/D3 levels and factors associated with systemic inflammation and melanoma survival in the Leeds Melanoma Cohort

Lower 25-hydroxyvitamin D-2/D-3 levels at melanoma diagnosis are associated with thicker primaries and poorer survival. We postulated that this might relate to the deleterious effect of systemic inflammation as 25-hydroxyvitamin D-2/D-3 levels are inversely associated with levels of C-reactive protein. 2,182 participants in the Leeds Melanoma Cohort (median follow-up 7.98 years) provided data on drug exposure, comorbidities and a serum 25-hydroxyvitamin D-2/D-3 level at recruitment. Factors reported to modify systemic inflammation (low vitamin D levels, high body mass index, use of aspirin or nonsteroidal anti-inflammatory drugs or smoking were tested as predictors of microscopic ulceration (in which primary tumors are inflamed) and melanoma-specific survival (MSS). Ulceration was independently associated with lower 25-hydroxyvitamin D-2/D-3 levels (odds ratio (OR)=0.94 per 10 nmol/L, 95% CI 0.88-1.00, p=0.05) and smoking at diagnosis (OR=1.47, 95% CI 1.00-2.15, p=0.04). In analyses adjusted for age and sex, a protective effect was seen of 25-hydroxyvitamin D-2/D-3 levels at diagnosis on melanoma death (OR=0.89 per 10 nmol/L, 95% CI 0.83-0.95, p<0.001) and smoking increased the risk of death (OR=1.13 per 10 years, 95% CI 1.05-1.22, p=0.001). In multivariable analyses (adjusted for tumor thickness) the associations with death from melanoma were low 25-hydroxyvitamin D-2/D-3 level at recruitment (<20 nmol/L vs. 20-60 nmol/L, hazard ratio (HR)=1.52, 95% CI 0.97-2.40, p=0.07) and smoking duration at diagnosis (HR=1.11, 95% CI 1.03-1.20, p=0.009). The study shows evidence that lower vitamin D levels and smoking are associated with ulceration of primary melanomas and poorer MSS. Further analyses are necessary to understand any biological mechanisms that underlie these findings. What's new? Vitamin D is known to affect immune function and suppress inflammation. In this study, the authors found that lower vitamin D levels at diagnosis and a history of smoking are both associated with a higher incidence of ulceration of primary melanoma, as well as with decreased survival. While a causal link hasn't yet been proven, the authors conclude that it would be prudent to suggest that melanoma patients should stop smoking, and that vitamin D depletion should be avoided.