Low circulating 25-hydroxyvitamin D level is associated with increased colorectal cancer mortality: a systematic review and dose–response meta-analysis

Epidemiological studies have suggested inconclusive associations between 25-hydroxyvitamin D (25(OH)D) and survival in patients with colorectal cancer (CRC). The aim of the present study was to quantitatively assess these associations. PubMed, EMBASE, and Web of Science databases were systematically searched for eligible studies. Subgroup analyses based on study geographic location, publication year, length of follow-up time, sample size, and stage were conducted to explore the potential sources of heterogeneity. Dose–response relationships and pooled hazard ratios (HR) for overall and CRC-specific survival comparing the highest versus the lowest categories of circulating 25(OH)D concentrations were assessed. Overall, 17 original studies with a total of 17,770 CRC patients were included. Pooled HR (95% confidence intervals) comparing highest versus lowest categories were 0.64 (0.55–0.72) and 0.65 (0.56–0.73) for overall and CRC-specific survival, respectively. Studies conducted in the U.S.A., with median follow-up time ≥ 8 years, larger sample size, and including stage I-III patients showed a more prominent association between 25(OH)D concentrations and overall survival. The dose–response analysis showed that the risk of all-cause mortality was reduced by 7% (HR = 0.93; 95% CI: 0.90, 0.95), and the risk of CRC-specific mortality was reduced by 12% (HR = 0.88; 95% CI: 0.84, 0.93) for each 20 nmol/l increment of 25(OH)D concentration. This meta-analysis provides evidences that a higher 25(OH)D concentration is associated with lower overall mortality and CRC-specific mortality.