Elevated plasma vitamin B12 levels and cancer prognosis: A population-based cohort study

Cancer Epidemiol. 2016 Feb;40:158-65. doi: 10.1016/j.canep.2015.12.007. Epub 2015 Dec 24.


Background: Elevated plasma vitamin B12 levels (cobalamin, Cbl) are associated with increased short-term cancer risk among patients referred for this laboratory measurement. We aimed to assess prognosis in cancer patients with elevated plasma Cbl.

Methods: We conducted a population-based cohort study using data from Danish medical registries during 1998-2014. The study included 25,017 patients with a cancer diagnosis and Cbl levels of 200-600 pmol/L (reference/normal range), 601-800 pmol/L and >800 pmol/L measured up to one year prior to diagnosis, and a comparison cohort of 61,988 cancer patients without a plasma Cbl measurement. Patients treated with Cbl were excluded. Survival probability was assessed using Kaplan-Meier curves. Mortality risk ratios (MRR) were computed using Cox proportional hazard regression, adjusted for age, sex, calendar year, cancer stage and comorbidity, scored using the Charlson comorbidity index.

Results: Survival probabilities were lower among patients with elevated Cbl levels than among patients with normal levels and among members of the comparison cohort [(1-year survival,%) Cbl: 200-600 pmol/L: 69.3%; 601-800 pmol/L: 49.6%; >800 pmol/L: 35.8%; comparison cohort: 72.6%]. Thirty-day mortality was elevated for patients with Cbl levels of 601-800 pmol/L or >800 pmol/L, compared to patients with levels of 200-600 pmol/L [(MRR (95% confidence interval): 601-800 pmol/L vs. 200-600 pmol/L: 1.9 (1.6-2.2); >800 pmol/L vs. 200-600 pmol/L: 2.7 (2.4-3.1)]. This association remained robust for 31-90-day and 91-365-day mortality, showing similar dose-response patterns.

Conclusion: Cancer patients with elevated Cbl levels had higher mortality than those with normal Cbl levels. These findings may have clinical significance for assessing the prognosis of cancer patients.

Keywords: Cancer; Cohort studies; Epidemiology; Mortality; Registries; Vitamin B 12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / diagnosis
  • Neoplasms / epidemiology*
  • Prognosis
  • Risk Assessment
  • Survival Rate
  • Vitamin B 12 / blood*
  • Young Adult


  • Biomarkers, Tumor
  • Vitamin B 12