Plasma 25-Hydroxyvitamin D and Risk of Non-Melanoma and Melanoma Skin Cancer: A Prospective Cohort Study

Abstract

Sun exposure is a major risk factor for skin cancer and is also an important source of vitamin D. We tested the hypothesis that elevated plasma 25-hydroxyvitamin D (25-OH-vitD) associates with increased risk of non-melanoma and melanoma skin cancer in the general population. We measured plasma 25-OH-vitD in 10,060 white individuals from the Danish general population. During 28 years of follow-up, 590 individuals developed non-melanoma skin cancer and 78 developed melanoma skin cancer. Increasing 25-OH-vitD levels, by clinical categories or by seasonally adjusted tertiles, were associated with increasing cumulative incidence of non-melanoma skin cancer (trend P=2 × 10(-15) and P=3 × 10(-17)) and melanoma skin cancer (P=0.003 and P=0.001). Multivariable adjusted hazard ratios of non-melanoma skin cancer were 5.04 (95% confidence interval (CI): 2.78-9.16) for 25-OH-vitD ≥50 vs. <25 nmol l(-1), and 4.02 (2.45-6.60) for top versus bottom tertile. Multivariable adjusted hazard ratios of melanoma skin cancer were 4.7 (0.96-23.3) for 25-OH-vitD ≥50 vs. <25 nmol l(-1), and 6.3 (1.38-28.8) for top versus bottom tertile. The absolute 20-year risk was 11% for non-melanoma skin cancer and 1.5% for melanoma skin cancer, in participants with age >60 years, 25-OH-vitD winter levels ≥50 nmol l(-1), and performing outdoor exercise. In conclusion, we show that increasing levels of 25-OH-vitD are associated with increased risk of non-melanoma and melanoma skin cancer.

Low Plasma 25-Hydroxyvitamin D and Risk of Tobacco-Related Cancer

“…Furthermore, as our cohort consists of white Danes living in Denmark with less sun exposure than those closer to the equator, our findings would be most relevant for individuals with a similar level of sun exposure and for similar 25(OH)D concentrations. The delay in measurement from 1981-1983 to 2009 -2010 could raise the concern of potential decay of plasma 25(OH)D, but several observations makes this highly unlikely: we noticed the expected seasonal variation of 25(OH)D concentrations; we found a strong association with skin cancer as expected with a reliable 25(OH)D measurement (27 ); median concentrations of plasma 25(OH)D across plasma samples from 3 different examinations on the same healthy participants with storage times of 10, 20, and 30 years were similar (27,28 ); previous studies have shown high stability during storage (40 ); the median concentration observed in our study of 16 ng/mL (41 nmol/L) was similar to that in comparable populations (16,19 ), and a low sample quality for the 25(OH)D measurement would tend to weaken rather than inflate an association. Finally, residual confounding cannot be ruled out as a potential explanation for our findings, because this is an observational study.…”

Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis

“…After applying inclusion criteria, 20 papers were left for analysis [25][26][27][28][29][30][38][39][40][41][42][43][44][45][46][47][48][49][50][51] (Fig. 1).…”

“…Four studies [28,[38][39][40] (392 CM cases overall) reported measures of melanoma risk across categories of increasing 25(OH)D serum levels: these were metaanalysed to yield a non-significant SRR of 1.46 (95% CI 0.60-3.53) for highest versus lowest categories (Fig. 2), with I 2 = 54%.…”

“…before the diagnosis of cancer. Instead, this is not the case for melanoma: in particular, the two studies that found an increased risk (with borderline statistical significance) are two cohort studies [28][29][30][31][32][33][34][35][36][37][38][39][40]; the nested case-control study also found an increased risk, although smaller [39]; while the two large-sized case-control studies found no association [29,38]. The case-control design is suboptimal when investigating the association between vitamin D and cancer incidence, as the tumour itself might reduce the 25(OH)D blood levels (although the mechanism is still unclear) [55], leading to a potential reverse causation bias [56].…”

“…The studies that tried to provide evidence on the effect of vitamin D on skin cancer risk have produced inconsistent results so far [25][26][27][28]. Other studies investigated the association of vitamin D blood levels with prognosis of CM, with results that, although inconclusive, seem to suggest a beneficial effect [29,30].…”