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

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. Skin cancers are the most common type of malignancies in Caucasian populations 1 and their incidence has risen worldwide over the past decades 2-4. Melanoma is the most lethal form of skin cancer 5 , with highest incidence rates observed in Australia and New Zealand, followed by Northern America and Europe, and the lowest rates in Asian and African populations 1. Although keratinocyte cancers (KCs), namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), have low mortality rate, they have relevant impact on quality of life and healthcare costs 6,7. The incidence of skin cancer has been expected to increase over the coming decades due to the increasing intensity of ultraviolet (UV) radiation received at the Earth's surface, which is caused by ozone depletion and global warming 8. Established risk factors for skin cancer include sun exposure 9, which is currently the only factor on which prevention can be based, pigmentary traits 10, and family history of skin cancer 11. However, some dietary factors, such as an antioxidant and anti-inflammatory-rich diet, have been suggested to

New Roles for Vitamin D Superagonists: From COVID to Cancer

“…Here ultraviolet B irradiation is a major risk factor and analysis of the relationship between serum calcidiol and melanoma is confounded by sun exposure. Importantly, no increased risk of melanoma occurred with vitamin D supplementation ( 130 ). Interestingly, several recent preclinical studies have suggested 7-dehydrocholesterol (a precursor of vitamin D) exerts anti-tumor activity in melanoma ( 131 ).…”

Prediagnostic serum 25-hydroxyvitamin D and melanoma risk

“…Laboratory results of 25(OH)D were provided in nmol/L on a continuous scale. We categorized 25 Health survey and registry data. Baseline measurements of height (to the nearest 1 cm) and weight (to the nearest 0.5 kg) were obtained by trained staff according to a standardized protocol.…”

“…Although laboratory studies provide a biological plausibility that an adequate level of 25(OH)D may inhibit cancer development, some recent studies have not found evidence of an association 20,21 , while others have reported an inverse association between 25(OH)D and cancer risk 22,23 . The three most recent meta-analyses of serum 25(OH)D and melanoma risk concluded that there is no association [24][25][26] . However, the two earlier Identification of cancer cases.…”

Systemic Photoprotection in Skin Cancer Prevention: Knowledge among Dermatologists

“…Furthermore, 1,25(OH) 2 D3 has been shown to reduce postirradiation edema, inflammation, and photocarcinogenesis in mouse skin [ 11 ]. In a recent systematic review and dose–response meta-analysis of prospective studies regarding vitamin D intake and skin cancer risk [ 12 ], the authors reported that, while intakes of dietary or supplemental vitamin D were not associated with the risk of melanoma and squamous cell carcinoma, high intakes of vitamin D from diet and supplements were slightly associated with basal cell carcinoma risk. Considering that vitamin D levels are mainly affected by exposure to the sun, a higher risk of skin cancer may be confounded by sun exposure [ 12 ].…”

“…In a recent systematic review and dose–response meta-analysis of prospective studies regarding vitamin D intake and skin cancer risk [ 12 ], the authors reported that, while intakes of dietary or supplemental vitamin D were not associated with the risk of melanoma and squamous cell carcinoma, high intakes of vitamin D from diet and supplements were slightly associated with basal cell carcinoma risk. Considering that vitamin D levels are mainly affected by exposure to the sun, a higher risk of skin cancer may be confounded by sun exposure [ 12 ]. Other antioxidants, such as astaxanthin and other molecules, fail to demonstrate the capacity to reduce new melanoma or NMSC formation [ 1 , 3 ].…”