Vitamin D insufficiency was found to be weakly linked to an increased incidence of cutaneous melanoma (CM), and lower vitamin D levels were associated with a less favorable Breslow tumor depth, according to authors of a systematic review and meta-analysis published in Melanoma Research.
CMis the fifth most common cancer in the United States and the most lethal skin cancer, requiring early detection and identification of risk factors to reduce adverse outcomes. Researchers sought to assess the relationship between vitamin D insufficiency and both the incidence and stage of CM, and between CM and levels of 25-hydroxy vitamin D (25[OH]D).
For their study, the researchers searched Cochrane Library, Google Scholar, Embase, Ovid Medline, and PubMed.gov from inception to July 2022, without language restriction, for cohort and case-control studies reporting on patients with CM with vitamin D insufficiency (<20 ng/dL) or mean 25(OH)D levels compared with healthy controls, or reporting on patients with CM and documented Breslow tumor depth or development of metastasis with vitamin D insufficiency.
The authors excluded abstract-only studies and studies that only reported data in multivariate analysis, failed to report accurately or in a standardized manner Breslow tumor depth in patients with CM, or only reported 25(OH)D levels in quartiles or quintiles. Also excluded were studies not using values <20 ng/dL as the standard for vitamin D insufficiency, studies failing to report mean levels, and studies lacking a control group.
Overall, they determined that 14 studies (all observational) were eligible for analysis. These were independently reviewed by 2 investigators who evaluated quality and risk of bias using a modified Newcastle-Ottawa Quality Assessment Tool for the observational, cohort, and cross-sectional studies. The authors excluded 1 study from meta-analysis for incomplete reporting. They noted 8 studies with moderate to high-risk of bias and 5 with low risk of bias. Quality of evidence was low for all included studies.
Employing a random effects model to evaluate CM incidence in the context of vitamin D levels, they performed a meta-analysis on 8 studies including 1895 patients and found no statistical significance in the relationship between mean vitamin D level and CM incidence (pooled standardized mean difference [SMD], −0.39; 95% CI, −0.80 to 0.01). In addition, they did not observe a statistically significant relationship between vitamin D levels and the presence of metastasis in pooled SMD from 2 studies including 408 patients (SMD, −0.13; 95% CI, −0.38 to 0.12). However, they noted that the pooled effect size showed individuals diagnosed with CM tended to have lower 25(OH)D levels (mean, 22.85 ng/mL) than those without CM (mean, 23.70 ng/mL).
A statistically significant relationship was found between CM incidence and vitamin D levels <20 ng/dL (pooled risk ratio [RR], 1.45; 95% CI, 1.04-2.02). Among the 8 studies evaluated (n=1299), 2 (n not noted) were determined to be outliers and consequently dropped from analysis. There was a statistically significant relationship between vitamin D level below 20 ng/dL and Breslow tumor depth below 1 mm. The authors noted a statistically significant relationship between mean vitamin D level below 20 ng/dL and Breslow tumor depth below 1 mm (2 studies, n=990; pooled RR, 0.69; 95% CI, 0.58-0.82). Tumor depth greater than or less than 1 mm was reported by 2 studies (n=238) and a fixed effects model was used to calculate pooled RR; the results (SMD, 0.19; 95% CI, 0.11-0.28) indicated that Breslow thickness was less likely to be below 1 mm when 25(OH)D levels were below 20 ng/dL.
There was no statistically significant correlation between vitamin D levels and the presence of metastasis (pooled SMD, −0.13; 95% CI, −0.38 to 0.12).
Limitations of this review and meta-analysis include the observational nature of all analyzed studies (ie, the lack of randomized controlled trials); the fact that the majority of included studies had a moderate to high risk for bias; the low quality of evidence for all studies; and the small sample size, which limited the assessment of vitamin D status as it related to the prognostic indicators of Breslow tumor depth and metastasis.
“We found low quality evidence with moderate risk of bias of a correlation between vitamin D insufficiency and increased incidence of CM; that vitamin D sufficiency is associated with a Breslow depth [below] 1 mm at the time of diagnosis of CM; and that Breslow depth [below] 1 mm at the time of diagnosis of CM is associated with lower 25(OH)D levels,” the authors concluded. “Given the lack of a decline in melanoma mortality along with the ease of measuring 25(OH)D levels, the clinical relevance of our finding may have an impact on future clinical practice,” they wrote. More evidence, they emphasized, is required to determine whether identification and treatment of vitamin D insufficiency can decrease the incidence of CM among high-risk patients.
References:
Shellenberger RA, Gowda S, Kurn H, Albright J, Mayo MH. Vitamin D insufficiency and serum levels related to the incidence and stage of cutaneous melanoma: a systematic review and meta-analysis. Melanoma Res. Published online May 18, 2023. doi:10.1097/CMR.0000000000000897
