Elevated plasma vitamin B12 levels as a marker for cancer: a population-based cohort study

Abstract

Background: A substantial proportion of patients referred for plasma vitamin B12 (cobalamin [Cbl]) measurement present with high Cbl levels, which have been reported in patients with different cancer types. However, the cancer risk among patients with newly diagnosed high Cbl levels has not been adequately examined.

Methods: We conducted this cohort study using population-based Danish medical registries. Patients referred for Cbl measurement with levels greater than the lower reference limit (≥200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009 using a database of laboratory test results covering the entire population. Data on cancer incidence (follow-up 1998-2010), Cbl treatment, and prior diagnoses were obtained from medical registries. Patients receiving Cbl treatment were excluded. Cancer risks were calculated as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), stratified by plasma Cbl levels. All statistical tests were two-sided.

Results: We identified 333 667 persons without prevalent cancer and not receiving Cbl treatment. Six percent had Cbl levels greater than the upper reference limit (≥601 pmol/L). Cancer risk increased with higher Cbl levels and was highest during the first year of follow-up (Cbl 601-800 pmol/L: SIR = 3.44, 95% CI = 3.14 to 3.76; Cbl >800 pmol/L: SIR = 6.27, 95% CI = 5.70 to 6.88; both P < .001). The risks were particularly elevated for hematological and smoking- and alcohol-related cancers for persons with high Cbl levels.

Conclusions: High Cbl levels were associated with the risk of subsequently diagnosed cancer, mostly within the first year of follow-up. This may have clinical implications for the interpretation of high Cbl levels.

Figure 1.

One-year risk of cancer in groups according to plasma cobalamin (Cbl) levels in 100 to 200 pmol/L intervals. The figure shows the 1-year standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs; vertical bars) disaggregated according to Cbl levels for hematological cancers (solid line), smoking- and alcohol-related cancers (dashed line), immune-related cancers (dotted/dashed line), and hormone-related cancers (dotted line). Note the logarithmic scale for standardized incidence ratio on the y-axis. The horizontal gray line indicates a standardized incidence ratio of 1. All statistical tests were two-sided.

Figure 2.

Risk of specific cancer types within the first year after plasma cobalamin (Cbl) measurement. The figure shows the 1-year standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) disaggregated according to Cbl levels: x: 200 to 600 pmol/L; o: 601 to 800 pmol/L; and □: greater than 800 pmol/L. The vertical gray line indicates standardized incidence ratio of 1. All statistical tests were two-sided.