Elevated Vitamin B12 Levels and Cancer Risk in UK Primary Care: A THIN Database Cohort Study

BACKGROUND: Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. However, the implications for early cancer detection in primary care have not been assessed. METHODS: Individuals with plasma B12 measurements were sampled from The Health Improvement Network primary care database, UK. Persons with low B12 levels were excluded together with persons with cancer or B12 treatment before date of B12 measurement. Incident cancer was the outcome of interest and was identified through Read codes. Individuals were disaggregated according to plasma B12 levels (unit: pmol/L): 150-600 (reference range values), 601-800, 801-1,000, and >1,000. RESULTS: Among the 757,185 persons who met the inclusion criteria, we identified 33,367 incident cancers during 2,874,059 years of follow-up. We found a higher 1-year cancer risk among the 25,783 (3.4%) persons with elevated B12 levels compared with those with normal B12 levels. After multivariable adjustment for lifestyle factors and social deprivation, persons with B12 >1,000 pmol/L had a 1-year incidence rate ratio of 4.72 (95% confidence interval: 3.99-5.58). The association showed a nonlinear dose-response pattern, and it remained robust in stratified analyses, including when reducing the risk of confounding by indication in subanalyses. The risks were particularly elevated for liver cancer, pancreas cancer, and myeloid malignancies among persons with elevated B12 levels. CONCLUSIONS: Elevated plasma B12 levels were associated with a higher 1-year cancer risk than normal B12 levels among persons seen in UK primary care, suggesting that some cancers may affect B12 metabolism. IMPACT: Elevated B12 may mark occult cancer.