Abstract
Recent studies have reported a link between elevated B12 levels and increased incidence of malignancies. In this study, we compare the association between B12 levels and adverse outcomes in colon cancer, including metastases and mortality. A globally federated multi-institutional database identified patients with colon cancer who had at least one B12 measurement within 1 year of diagnosis. Patients were stratified by B12 status (normal: 300-1,000, elevated: >1,000, and low: <300 pg/mL). Median overall survival (mOS) was compared via log-rank test and Cox proportional hazards models. The incidence of cancer metastases and elevated liver enzymes within 1 year of diagnosis was analyzed and compared using risk ratios. Further gene expression analysis of 283 colon cancer samples from The Cancer Genome Atlas (TCGA) and 304 normal colon tissues from the Genotype-Tissue Expression (GTEx) project was performed. A total of 37,106 patients were identified by TriNetX. High B12 (n = 6,523; mOS = 59.4 months) was associated with a decreased mOS compared with normal (n = 23,965; mOS = 129.8 months) and low (n = 5,167; mOS = 137.3 months) B12 patients. Patients with elevated B12 had higher metastatic involvement and tumor stage at diagnosis and a higher 1-year incidence of all metastases, liver, lung, and peritoneal metastases [risk ratio with 95% confidence intervals of 1.30 (1.24-1.36), 1.56 (1.45-1.68), 1.43 (1.27-1.61), 1.39 (1.24-1.55), respectively]. Gene expression analysis of TCGA and GTEx identified the expression of the B12-dependent methionine synthase (MTR) to be elevated in colon cancer tissue, and increased MTR expression was associated with decreased colon cancer survival (65.8 months vs. undefined). These findings identify the potential clinical relevance of B12 as a biomarker for colon cancer metastases and survival. SIGNIFICANCE: Elevated B12 has been reported to be associated with increased cancer incidence; however, its role as a prognostic marker in colon cancer is unclear. In this multi-institutional study investigating clinical outcomes of patients with colon cancer, we demonstrate elevated B12 as a potential biomarker for colon cancer metastases and survival.