Winslow UC, et al. - Experts sought to test the preassumption that genetically high plasma 25-hydroxyvitamin D 25(OH)D protects against nonmelanoma skin cancer (NMSC). They did not note the genetically determined high 25(OH)D levels to protect against NMSC. An association of high plasma 25(OH)D concentrations with an observational high risk of NMSC was seen. Therefore, rather than causality, the observational association likely reflected confounding by sun exposure.

Methods

• Authors 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 4 genetic variants near DHCR7 and CYP2R1 associated with 25(OH)D concentrations.
• Using an instrumental variable approach, they tested the correlation between plasma 25(OH)D levels and NMSC observationally and between genetically determined 25(OH)D levels and NMSC.

Results

• Results suggested that 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 < 25 nmol L^-1.
• Researchers noted that genetic variants around DHCR7 and CYP2R1 were associated with up to 8·2 nmol L^-1 higher 25(OH)D concentrations (F = 314).
• Findings demonstrated that for NMSC, 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), with a corresponding observational multivariable adjusted OR of 1·13 (95% CI 1·10–1·17).