25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose\u2013response meta-analysis of prospective studies

Yahya Mahamat-Saleh,Sabrina Schlesinger,Dagfinn Aune

doi:10.1038/s41598-020-70078-y

Abstract

Sun exposure is a major environmental risk factor for skin cancers and is also an important source of vitamin D. However, while experimental evidence suggests that vitamin D may have a protective effect on skin cancer risk, epidemiologic studies investigating the influence of 25-hydroxyvitamin D (25(OH)D) level and/or vitamin D intake on skin cancer risk are conflicting. A systematic review and dose–response meta-analyses of prospective studies was conducted to clarify these associations. Relevant studies were identified by searching the PubMed database up to 30th August 2019. Random effects dose–response meta-analyses were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). Overall, thirteen prospective studies were included. Circulating level of 25(OH)D was associated with higher risks of melanoma (SRR (95% CI) per 30 nmol = 1.42 (1.17–1.72)) and keratinocyte cancer (KC) (SRR (95% CI) per 30 nmol/L = 1.30 (1.13–1.49)). The SRR (95% CI) per 30 nmol/L increase in 25(OH) D level was 1.41 (1.19–1.67), and 1.57 (0.64–3.86), for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), respectively. However, while we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type. This meta-analysis suggests positive associations between circulating 25(OH)D level and risk of melanoma and KC, however, this finding is most likely confounded by sun exposure. We found no associations between vitamin D intake skin cancers, except positive associations with BCC risk.

Highlights

Sun exposure is a major environmental risk factor for skin cancers and is an important source of vitamin D
We found that 25(OH) D levels were associated with higher risk of keratinocyte cancer (KC) (SRR per 30 nmol/L increment = 1.30; 95% confidence intervals (CIs) = 1.13–1.49, I 2 = 86%, Pheterogeneity = 0.001) (Table 1, Fig. 1B)
While we observed positive associations between vitamin D intake (SRR per 100 IU/day increment = 1.04 for dietary, 1.02 for supplemental and 1.02 for total vitamin D) and risk of basal cell carcinomas (BCCs) (Fig. 6A), we found no significant associations between vitamin D intake and risk of squamous cell carcinomas (SCCs) (SRR per 100 IU/day increment was 1.02 for dietary, 0.98 for supplemental and 0.99 for total vitamin D) (Fig. 6B)

Summary

Introduction

Sun exposure is a major environmental risk factor for skin cancers and is an important source of vitamin D. While we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type This meta-analysis suggests positive associations between circulating 25(OH) D level and risk of melanoma and KC, this finding is most likely confounded by sun exposure. Since the publication of this meta-analysis, several prospective studies have been published on vitamin D status and skin c ancer[31,32,33,34], and no previous meta-analysis has investigated the potential nonlinear dose–response relationship between 25(OH)D status and skin cancer risk. We conducted a systematic review and dose–response meta-analysis of prospective studies to investigate the association between vitamin D exposure (from diet, supplements and circulating level) and risk of skin cancer, including melanoma and KC (BCC and SCC)

Methods

Results

Conclusion