High plasma 25-hydroxyvitamin D and high risk of nonmelanoma skin cancer: a Mendelian randomization study of 97 849 individuals

Winsløw, Ulrik; Nordestgaard, Børge G.; Afzal, Shoaib

doi:10.1111/bjd.16127

Cited by 25 publications

(22 citation statements)

References 49 publications

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“…It can be challenging to interpret the univariable MR association between 25(OH)D and skin cancers (i.e. melanoma and keratinocyte cancers (KC)) given the potential confounding pathways through pigmentation and skin aging which are established risk factors for these cancers 28 . The univariable MR associations suggest higher 25(OH)D levels increase risk of basal cell carcinoma (BCC) (OR = 1.16 [1.04-1.28], while the OR for melanoma was smaller with confidence intervals overlapping 1 (OR 1.05 [0.90-1.23]).…”

Section: Resultsmentioning

confidence: 99%

A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Ong¹,

Dixon-Suen²,

Han³

et al. 2021

Nat Commun

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Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

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Section: Resultsmentioning

confidence: 99%

A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Ong¹,

Dixon-Suen²,

Han³

et al. 2021

Nat Commun

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show abstract

“…Ten studies reported a RR estimate comparing NMSC risk among those in the highest vs. lowest category of serum/plasma 25(OH)D concentration ( Table 1 ) [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Of these, five were conducted in the USA, two in Denmark, and one each in Australia, Brazil, and Poland.…”

Section: Resultsmentioning

confidence: 99%

Vitamin D and the Risk of Non-Melanoma Skin Cancer: A Systematic Literature Review and Meta-Analysis on Behalf of the Italian Melanoma Intergroup

Caini¹,

Gnagnarella

Stanganelli

et al. 2021

Cancers

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We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February 2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61–4.56), although with large heterogeneity across studies (I2 = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the VDR and VDBP genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation.

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“…In our study, after adjustment for the effect of possible confounding factors in multivariate logistic regression, vitamin D level could not independently predict the occurrence of SCC. It seems that, as Winsløw et al noted, the level of vitamin D in our population not consuming supplements is a surrogate for their amount of sun exposure, which per se has an established role in skin cancer[20]. Thus this vitamin…”

mentioning

confidence: 70%

Relationship Between Level of Serum 25-Hydroxyvitamin D and Risk of Squamous Cell Carcinoma in an Iranian Population

Hosseini

Salarvand

Ehsani

et al. 2019

Dermatol Pract Concept

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Background: The relationship between vitamin D and skin squamous cell carcinoma (SCC) is not well defined. Objective: To investigate the relationship between vitamin D levels and the incidence of skin SCC for the first time in Iran. Methods and Study Design: In this case-control study, 126 subjects were enrolled (63 in each group) out of referents to Razi Skin Hospital in Tehran in 2014. The risk factors for cancer gathered by self-reported questionnaires and blood samples were obtained to measure the level of 25-hydroxyvitamin D. Multivariate logistic regression was used to neutralize the effect of confounding factors. Results: Cases of SCC were more likely to be in men, older than 49 years and working in an outdoor environment, and with longtime exposure to sunlight and a personal history of skin cancers. Family history of skin cancer and of cigarette smoking were not significantly related to SCC. In the SCC and control groups, 69.8% and 31.7%, respectively, had sufficient levels of vitamin D (P < 0.001). Mean level of 25-hydroxyvitamin D was 40.99 ng/mL in the SCC group and 26.34 ng/mL in the control group (P < 0.05). In the unadjusted model, the level of vitamin D as a continuous variable was positively related to SCC risk. In the adjusted model, vitamin D did not independently predict the likelihood of SCC. Conclusion: Vitamin D level and SCC risk are directly related, although not in an independent fashion. Indeed, this relation is severely confounded by exposure to sunlight, which was evidenced by an increased vitamin D level in the people working outside and the higher prevalence of SCC in the same population.

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High plasma 25-hydroxyvitamin D and high risk of nonmelanoma skin cancer: a Mendelian randomization study of 97 849 individuals

Abstract: Genetically determined high 25(OH)D levels did not appear to protect against NMSC, whereas high plasma 25(OH)D concentrations were associated with an observational high risk of NMSC. Thus, the observational association likely reflects confounding by sun exposure rather than causality.

Cited by 25 publications

References 49 publications

A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Vitamin D and the Risk of Non-Melanoma Skin Cancer: A Systematic Literature Review and Meta-Analysis on Behalf of the Italian Melanoma Intergroup

Relationship Between Level of Serum 25-Hydroxyvitamin D and Risk of Squamous Cell Carcinoma in an Iranian Population

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