Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival

Abstract

Purpose: Although vitamin D inhibits pancreatic cancer proliferation in laboratory models, the association of plasma 25-hydroxyvitamin D [25(OH)D] with patient survival is largely unexplored.

Patients and methods: We analyzed survival among 493 patients from five prospective US cohorts who were diagnosed with pancreatic cancer from 1984 to 2008. We estimated hazard ratios (HRs) for death by plasma level of 25(OH)D (insufficient, < 20 ng/mL; relative insufficiency, 20 to < 30 ng/mL; sufficient ≥ 30 ng/mL) by using Cox proportional hazards regression models adjusted for age, cohort, race and ethnicity, smoking, diagnosis year, stage, and blood collection month. We also evaluated 30 tagging single-nucleotide polymorphisms in the vitamin D receptor gene, requiring P < .002 (0.05 divided by 30 genotyped variants) for statistical significance.

Results: Mean prediagnostic plasma level of 25(OH)D was 24.6 ng/mL, and 165 patients (33%) were vitamin D insufficient. Compared with patients with insufficient levels, multivariable-adjusted HRs for death were 0.79 (95% CI, 0.48 to 1.29) for patients with relative insufficiency and 0.66 (95% CI, 0.49 to 0.90) for patients with sufficient levels (P trend = .01). These results were unchanged after further adjustment for body mass index and history of diabetes (P trend = .02). The association was strongest among patients with blood collected within 5 years of diagnosis, with an HR of 0.58 (95% CI, 0.35 to 0.98) comparing patients with sufficient to patients with insufficient 25(OH)D levels. No single-nucleotide polymorphism at the vitamin D receptor gene met our corrected significance threshold of P < .002; rs7299460 was most strongly associated with survival (HR per minor allele, 0.80; 95% CI, 0.68 to 0.95; P = .01).

Conclusion: We observed longer overall survival in patients with pancreatic cancer who had sufficient prediagnostic plasma levels of 25(OH)D.

Fig 1.

Overall survival curves by prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] among patients with pancreatic cancer.

Fig 2.

Forest plot and meta-analysis of hazard ratios (HRs) for death among patients with pancreatic cancer, comparing those with sufficient levels of 25-hydroxyvitamin D with those with insufficient levels in the Health Professionals Follow-up Study (HPFS), Nurses' Health Study (NHS), Physicians’ Health Study (PHS), Women’s Health Initiative (WHI), and Women’s Health Study (WHS). Solid squares and horizontal lines correspond to the cohort-specific multivariable-adjusted hazard ratios and 95% CIs. Area of the solid square reflects the cohort-specific weight (inverse of the variance). Diamond represents the meta-analysis multivariable-adjusted HR and 95% CI. Vertical line indicates an odds ratio of 1.0. HRs adjusted for age at diagnosis, race and ethnicity (white, black, other, unknown), smoking status (never, past, current, or missing), month of blood draw (2-month intervals), stage at diagnosis (localized, locally advanced, metastatic, or unknown), and year of diagnosis (1984-2000 or 2001-2008).