Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

Abstract

Purpose We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome. Patients and Methods We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype–25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs). Results We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008). Conclusion In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.

Vitamin D Deficiency and Increased Risk of Bladder Carcinoma: A Meta-Analysis

“…The findings from the meta-analysis provide strong epidemiological evidence for the important role of vitamin D in bladder carcinogenesis. There are several studies published to assess the role of vitamin D deficiency on the prognosis of cancer patients, and vitamin D deficiency may decrease the overall survival of cancer patients, such as colorectal cancer [28]. However, there is no study performed to assess the relation of vitamin D deficiency with prognosis of bladder carcinoma patients, and there is still lack of clinical evidence.…”

Vitamin D and Cancer Risk and Mortality: State of the Science, Gaps, and Challenges

“…A U-shaped relationship was observed for prediagnostic 25(OH)D and breast cancer mortality in the Swedish Malmo cohort (81). On the basis of blood samples taken after diagnosis, a higher level of 25(OH)D was associated with a lower colorectal cancer mortality (82,83), ovarian cancer mortality (84), and Merkel cell carcinoma mortality (although not significant) (85). Higher postdiagnostic 25(OH)D status was also associated with significantly improved pancreatic cancer survival in 1 study (86).…”

Vitamin D, Inflammation, and Colorectal Cancer Progression: A Review of Mechanistic Studies and Future Directions for Epidemiological Studies

“…Both meta-analyses showed that patients with colorectal cancer with high vitamin D levels compared with patients with low vitamin D levels had a significantly reduced overall and colorectal cancer-specific mortality (4,5). One recent additional study that focused on postoperative vitamin D levels also showed that vitamin D status was inversely associated with both overall and colorectal cancer-specific mortality (9). Table 1 provides details of all published prospective studies on vitamin D status and colorectal cancer survival.…”