High plasma 25-hydroxyvitamin D and high risk of nonmelanoma skin cancer: a Mendelian randomization study of 97 849 individuals
Winsløw UC, Nordestgaard BG, Afzal S
The British journal of dermatology · 25 citations
How it was studied
- Design
- Cohort study (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Hjerteforeningen
- University or hospital
- Gentofte Hospital
- University or hospital
- Herlev and Gentofte Hospital
Based on 3 listed funder(s).
Publication
- Published
- 2017-11-16 · Br J Dermatol · vol. 178 · issue 6 · pp. 1388–1395
- Publisher
- Oxford University Press
- Cited
- 50 citations · more than 78% of similar papers · 1.2× the field average
- References
- 53 works
- Access
- Paywalled
- Research areas
- Vitamin D Research Studies · Thyroid Cancer Diagnosis and Treatment · Skin Protection and Aging
- Keywords
- Vitamin D and neurology, Skin cancer, Hazard ratio, Internal medicine, Confidence interval, Mendelian randomization, Medicine, Odds ratio, Population, Endocrinology, Cancer, Biology, Genetics, Genotype, Genetic variants, Gene
- MeSH
- humans, skin neoplasms, vitamin d, risk factors, cohort studies, sunlight, environmental exposure, genotype, adult, aged, aged, 80 and over, middle aged, denmark, female, male, young adult, mendelian randomization analysis
3 authors
From DK
- Ulrik WinsløwUniversity of Copenhagen; Copenhagen University Hospital; Gentofte Hospital
- Børge Grønne NordestgaardUniversity of Copenhagen; Copenhagen University Hospital; Gentofte Hospital
- Shoaib Afzal · correspondingUniversity of Copenhagen; Copenhagen University Hospital; Gentofte Hospital
Abstract
Background
High plasma 25-hydroxyvitamin D [25(OH)D] concentration has been associated observationally with a high risk of nonmelanoma skin cancer (NMSC), whereas many studies suggest that vitamin D could have a protective effect against cancer. The true association between vitamin D and risk of skin cancer remains unclear.
Objectives
To test the hypothesis that genetically high plasma 25(OH)D protects against NMSC.
Methods
We included 103 084 individuals from the Danish general population, of whom 35 298 had plasma 25(OH)D measured and 97 849 were genotyped for four genetic variants near DHCR7 and CYP2R1 associated with 25(OH)D concentrations. We tested the association between plasma 25(OH)D levels and NMSC observationally and between genetically determined 25(OH)D levels and NMSC, using an instrumental variable approach.
Results
Multivariate-adjusted hazard ratios of NMSC were 3·27 [95% confidence interval (CI) 2·22-4·84] for plasma 25(OH)D ≥ 50 nmol L-1 vs. -1 . Genetic variants around DHCR7 and CYP2R1 were associated with up to 8·2 nmol L-1 higher 25(OH)D concentrations (F = 314). The odds ratio (OR) for a genetically determined 20 nmol L-1 higher plasma 25(OH)D was 1·11 (95% CI 0·91-1·35) for NMSC, with a corresponding observational multivariable adjusted OR of 1·13 (95% CI 1·10-1·17).
Conclusions
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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