Circulating 25-Hydroxyvitamin D, VDR Polymorphisms, and Survival in Advanced Non-Small-Cell Lung Cancer

Purpose We showed previously that in early-stage non-small-cell lung cancer (NSCLC), serum vitamin D levels and VDR polymorphisms were associated with survival. We hypothesized that vitamin D levels and VDR polymorphisms may also affect survival among patients with advanced NSCLC. Patients and Methods We evaluated the relationship between circulating 25-hydroxyvitamin D levels; VDR polymorphisms, including Cdx-2 G > A (rs11568820), Fokl C > T (rs10735810), and BsmI C > T (rs144410); and overall survival among patients with advanced NSCLC. Analyses of survival outcomes were performed using the log-rank test and Cox proportional hazards models, adjusting for sex, stage, and performance status. Results There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the Fokl polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = .005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival ( adjusted hazard ratio for two or more v zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = .0008). On haplotype analysis, the G-T-C (Cdx-2-Fokl-Bsml) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (adjusted hazard ratio, 1.61; 95% CI, 1.21 to 2.14; P = .001). Conclusion There was no main effect of vitamin D level on overall survival in the advanced NSCLC population. The T allele of the VDR Fokl > T polymorphism and the G-T-C (Cdx-2- Fokl-Bsml) haplotype were associated with worse survival.