Prediagnostic Serum Vitamin D, Vitamin D Binding Protein Isoforms, and Cancer Survival

Abstract

Background

Higher circulating vitamin D has been associated with improved overall cancer survival, but data for organ-specific cancers are mixed.

Methods

We examined the association between prediagnostic serum 25-hydroxyvitamin D [25(OH)D], the recognized biomarker of vitamin D status, and cancer survival in 4038 men and women diagnosed with 1 of 11 malignancies during 22 years of follow-up (median = 15.6 years) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Multivariable-adjusted proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between baseline 25(OH)D concentration and subsequent cancer survival; we also stratified on the common vitamin D binding protein isoforms (Gc1f, Gc1s, and Gc2) defined by two single-nucleotide polymorphisms (rs7041 and rs4588) in the vitamin D binding protein gene GC. All P values were 2-sided.

Results

Higher 25(OH)D concentrations were associated with greater overall cancer survival (HR for cancer mortality = 0.83, 95% CI = 0.70 to 0.98 for highest vs lowest quintile; P_trend = .05) and lung cancer survival (HR = 0.63, 95% CI = 0.44 to 0.90; P_trend = .03). These associations were limited to cases expressing the Gc2 isoform (HR = 0.38 for Gc2-2, 95% CI = 0.14 to 1.05 for highest vs lowest quintile; P_trend = .02; and HR = 0.30 for Gc1-2/Gc2-2 combined, 95% CI = 0.16 to 0.56; P_trend < .001 for overall and lung cancer, respectively).

Conclusions

Higher circulating 25(OH)D was associated with improved overall and lung cancer survival. As this was especially evident among cases with the genetically determined Gc2 isoform of vitamin D binding protein, such individuals may gain a cancer survival advantage by maintaining higher 25(OH)D blood concentrations.