Prediagnostic serum 25-hydroxyvitamin D and melanoma risk

Jo S Stenehjem,Tom K Grimsrud,Judy R Rees,Trude E Robsahm,Marit B Veierød,Per M Thorsby,Ronnie Babigumira,Bjørn Johnsen,Nathalie C Støer,Reza Ghiasvand,Lill Tove Nilsen

doi:10.1038/s41598-020-77155-2

Abstract

Previous studies of serum 25-hydroxyvitamin D (25(OH)D) in relation to melanoma have shown conflicting results. We conducted a nested case–control study of 708 cases and 708 controls, using prediagnostically collected serum, to study 25(OH)D and melanoma risk in the population-based Janus Serum Bank Cohort. Stratified Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for ultraviolet radiation (UVR) indicators and stratified by ambient UVB of residence and body mass index (BMI). Non-linear associations were studied by restricted cubic splines. Missing data were handled with multiple imputation by chained equations. We found an HR of melanoma risk of 1.01 (95% CI: 0.99, 1.04) and an HRimputed of 1.02 (95% CI: 1.00, 1.04) per 5-nmol/L increase. The spline model showed exposure-risk curves with significantly reduced melanoma risk between 60 and 85 nmol/L 25(OH)D (reference 50 nmol/L). Non-significant J-shaped curves were found in sub-analyses of subjects with high ambient UVB of residence and of subjects with BMI < 25 kg/m2. Our data did not yield persuasive evidence for an association between 25(OH)D and melanoma risk overall. Serum levels within the medium range might be associated with reduced risk, an association possibly mediated by BMI.

Highlights

Incidence and mortality rates of cutaneous melanoma are increasing in fair-skinned populations worldwide[1]
The study research file was created by linkage of the Janus Cohort to Statistics Norway, the Norwegian National Population Register and the Cancer Registry of Norway (CRN) by the use of the 11-digit personal identification number assigned to all Norwegian citizens
body mass index (BMI), BSA, lifetime ambient UVB, sunburns, sunbathing vacations, solarium use, occupational ultraviolet radiation (UVR) and physical activity were comparable between cases and controls

Summary

Introduction

Incidence and mortality rates of cutaneous melanoma (hereafter melanoma) are increasing in fair-skinned populations worldwide[1]. Prospective studies have reported increased melanoma risk with increasing prediagnostic 25(OH)D serum levels[34,35,36,37,38], most likely due to confounding by UVR exposure[25,35,38]. The prospective studies vary in sample size, adjustment for UVR exposure, whether both sexes were studied, previous cancer history, and whether the melanoma cases were invasive or in situ. No study has prospectively examined the 25(OH)D-melanoma association by ambient UVB of residence, BMI, anatomical site and histological subtype. We used stored sera from the population-based and prospective Janus Serum Bank Cohort (hereafter Janus Cohort) to examine the association between prediagnostic 25(OH)D and melanoma risk with adjustment for UVR indicators. We aimed to assess the 25(OH)D-melanoma association with nonlinear models, and by stratification on ambient UVB of residence, BMI, anatomical site and histological subtype

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Conclusion