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

Int J Cancer. 2015 Jun 15;136(12):2890-9. doi: 10.1002/ijc.29334. Epub 2014 Dec 13.

Abstract

Lower 25-hydroxyvitamin D2 /D3 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 D2 /D3 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 D2 /D3 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 D2 /D3 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 D2 /D3 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 D2 /D3 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.

Keywords: inflammation; melanoma; smoking; survival; vitamin D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D 2 / blood*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspirin / therapeutic use
  • Calcifediol / blood*
  • Comorbidity
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / blood*
  • Inflammation / drug therapy
  • Inflammation / epidemiology
  • Male
  • Melanoma / blood*
  • Melanoma / drug therapy
  • Melanoma / epidemiology
  • Middle Aged
  • Multivariate Analysis
  • Smoking / blood
  • Smoking / epidemiology
  • Survival Analysis
  • Treatment Outcome
  • Ulcer / blood
  • Ulcer / epidemiology
  • United Kingdom / epidemiology
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • 25-Hydroxyvitamin D 2
  • Calcifediol
  • Aspirin