Association of Low Serum Vitamin B12 Concentration with Colorectal Cancer Risk and All-Cause Mortality: A Global Multi-Institutional Retrospective Cohort Study.
TL;DR
Low serum vitamin B12 was associated with higher all-cause mortality; its association with CRC was less robust at longer landmarks; the CRC finding requires prospective confirmation with serial B12 measurements.
Abstract
Background
The association between vitamin B12 deficiency and colorectal cancer (CRC) risk remains uncertain. We evaluated the association between low serum vitamin B12 concentration (<200 pg/mL) and CRC incidence and all-cause mortality, using a midrange reference group (400-600 pg/mL).
Methods
In this retrospective propensity score-matched cohort study, adults with serum B12 measurements between 2006 and 2020 were identified from the TriNetX Global Collaborative Network. Patients with any neoplasm diagnosis within 5 years before the index date (first B12 measurement) were excluded. Patients with B12 <200 pg/mL were matched 1:1 to those with 400-600 pg/mL and followed for up to 10 years. Time-stratified, landmark, subgroup, E-value, and outcome-control analyses were performed.
Results
After matching, 184,126 pairs were included. Low serum B12 was associated with higher CRC risk (HR 1.16; 95% CI, 1.09-1.23) and all-cause mortality (HR 1.16; 95% CI, 1.14-1.18). The CRC association persisted at the 2-year landmark (HR 1.16; 95% CI, 1.07-1.26) but attenuated at the 3-year (HR 1.07; 95% CI, 0.98-1.18) and 5-year (HR 1.12; 95% CI, 0.99-1.25) landmarks, whereas all-cause mortality remained elevated across all landmarks. The appendicitis negative control was null (HR 0.92; 95% CI, 0.84-1.02), whereas clavicle fracture was weakly positive (HR 1.08; 95% CI, 1.01-1.16).
Conclusions
Low serum vitamin B12 was associated with higher all-cause mortality; its association with CRC was less robust at longer landmarks. IMPACT The mortality association was more robust; the CRC finding requires prospective confirmation with serial B12 measurements.