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

Abstract

Epidemiological studies have suggested inconclusive associations between 25-hydroxyvitamin D (25(OH)D) and survival in patients with colorectal cancer (CRC). The aim of this 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 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 17770 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 USA, 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.

The association between preoperative 25-OH vitamin D levels and postoperative complications in patients undergoing colorectal cancer surgery

“…Our secondary outcome was to evaluate the effect of 25-OH vitamin D levels on histopathological grading and pTNM staging based on the fact that decreased 25-OH vitamin D levels are linked with poor survival in colorectal cancer patients [ 36 ]. Vitamin D levels were not related to histopathological grading in our study.…”

Role of Vitamin D in Colorectal Cancer: A Holistic Approach and Review of the Clinical Utility

“…A nested case-control study by Chandler et al included 274 female CRC cases and 274 female controls and followed the study population for 16.3 years to find out that those with 25(OH)D levels above 29 ng/mL were seen to have the highest reduction in the incidence and mortality with CRC [ 29 ]. The serum level of vitamin D and its effect on CRC-related mortality have also been highlighted by the dose-response analysis involving 17,700 participants from 18 studies by Wu et al The study found a 12% lower risk of colorectal-specific mortality and a 7% reduction in the risk of all-cause mortality with an increase of every 20 nmol/L of 25(OH)D [ 30 ]. Moreover, data from 17 cohorts, including 5706 CRC patients and 7107 control participants, were used in a study by McCullough et al and showed that the most favorable concentration of 25(OH)D for risk reduction of CRC was 75-100 nmol/L, which is higher than the current Institute of Medicine (IOM) recommendations.…”

“…The overall survival of patients with CRC is directly related to higher circulating levels of 25(OH)D. With this reduction in the all-cause and CRC-specific mortality, 25(OH)D can be an excellent protective agent that could positively affect the prognosis in these patients [ 30 ]. 25(OH)D-derived analogs have been developed to provide more potent antineoplastic effects and counter the unwanted calcemic side effects that have been a problem with using 25(OH)D alone as a treatment for cancer [ 35 ].…”

Transcriptomic analysis reveals that combinations of vitamins A, D2, and D3 have synergistic effects in HCT-116 colon cancer cells by altering the expression of genes involved in multiple canonical pathways including apoptosis, regulation of the...

“…The risk of breast, colorectal, gastric, prostate, and other cancers is increased in patients with a vitamin D deficiency, and for gastric cancer, lower vitamin D levels are associated with a poor prognosis [9][10][11][12][13][14][15]. Colorectal cancer patients with an elevated serum vitamin D level and intake had a better prognosis, and showed improved survival and reduced recurrence [7,[13][14][15][16][17][18][19].…”