Background: Vitamin D may inhibit tumor progression by suppressing metastasis, proliferation, and angiogenesis. The vitamin D binding protein (DBP) is the primary carrier of circulating vitamin D compounds and functions in actin scavengering, macrophage activation, and neutrophil chemotaxis. Little is known about the association between vitamin D, DBP, and lung cancer survival. We investigated the association between serum concentrations of 25-hydroxyvitamin D (25(OH)D), DBP, and lung cancer mortality in 500 lung cancer cases from the ATBC Study.

Methods: Serum concentrations of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free circulating vitamin D, were measured in fasting blood samples collected at baseline. Hazards ratios (HR) and 95% confidence intervals (CI) were used to estimate survival by quartiles of 25(OH)D, DBP, and the 25(OH)D:DBP molar ratio.

Results: Median survival time was 0.5 years (IQR: 0.1 - 1.1) for 428 cases that died from lung cancer and 1.7 years (IQR: 0.1 - 7.8) for 72 lung cancer survivors. Median serum concentrations (nmol/L) of 25(OH)D and DBP were 33 (IQR: 20-50) and 5951 (IQR: 4725-7196), respectively, for lung cancer deaths and 37 (IQR: 22-52) and 5431 (IQR: 4600-7151), respectively, for lung cancer survivors. In multivariable adjusted models, higher concentrations of serum 25(OH)D were associated with a small but not statistically significant increase in lung cancer mortality (Q4 vs. Q1 HR = 1.20; 95% CI: 0.90, 1.60). Survival was not associated with higher serum concentrations of DBP (Q4 vs. Q1 HR = 1.01; 95% CI: 0.76, 1.34). A higher 25(OH)D:DBP molar ratio was associated with a slightly reduced risk of mortality, although not significant (Q4 vs. Q1 HR = 0.87; 95% CI: 0.65, 1.18). DBP concentration did not modify the association between 25(OH)D or the 25(OH)D:DBP molar ratio and lung cancer survival. In histology-specific analyses, elevated concentrations of 25(OH)D was associated with higher mortality in squamous cell carcinomas (HR = 1.47; 95% CI: 0.82, 2.65) and adenocarcinomas (HR = 1.42; 95% CI: 0.33, 6.05), but reduced mortality in small cell carcinomas (HR = 0.62; 95% CI: 0.18, 2.10). A higher 25(OH)D:DBP molar ratio was associated with higher mortality for squamous cell tumors (HR = 1.28; 95% CI: 0.68, 2.40), and lower mortality for adenocarcinomas (HR = 0.10; 95% CI: 0.02, 0.57) and small cell tumors (HR = 0.52; 95% CI: 0.12, 2.18). Associations between serum DBP and mortality were similar across histologic types.

Conclusion: Higher vitamin D status was weakly associated with lung cancer survival and DBP was unrelated to survival; however, a higher 25(OH)D:DBP molar ratio indicative of unbound or “free” vitamin D may be related to increased adenocarcinoma and possibly small cell carcinoma survival. The findings should be evaluated in other longitudinal studies.

Citation Format: Gabriella M. Anic, Stephanie J. Weinstein, Satu Männistö, Demetrius Albanes. Serum 25-hydroxyvitamin D, vitamin D binding protein, and lung cancer survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2180. doi:10.1158/1538-7445.AM2014-2180