High post-surgery vitamin D levels linked with increased survival in colon cancer

1. In patients with Stage I-III colorectal cancer, higher postoperative serum 25-hydroxy vitamin D levels were associated with decreased cancer-specific mortality as well as overall mortality. 

2. There were significant interactions between serum vitamin D levels and polymorphisms in the vitamin D receptor gene that were associated with overall survival, which may indicate a causal relationship between vitamin D level and survival. 

Evidence Rating: 2 (Good)

Study Rundown: Pre-treatment levels of serum vitamin D have been previously linked to survival in colorectal cancer (CRC).  However, because vitamin D is a hormone involved in a wide variety of physiologic processes, establishing a causal inference is difficult.  In this study, the authors prospectively assessed the post-operative serum levels of vitamin D in Scottish patients with stage I to III CRC.  The authors also performed a meta-analysis of their data along with four prior studies examining serum vitamin D levels and CRC survival.  They found that there was a significant benefit in both CRC-specific and overall survival for patients with higher serum vitamin D levels as compared to those with lower levels.  In order to strengthen a causal relationship, the study also addressed reverse causation, an important confounder, by testing for interactions between serum vitamin D levels and polymorphisms at the vitamin D receptor (VDR) locus.  While there were no associations between survival and individual VDR SNPs, overall survival was significantly associated with interactions between vitamin D levels and VDR SNPs.  This study was limited in the fact that serum vitamin D levels were sampled only once, and moreover, at times varying from 53 to 200 days postoperatively.

Click to read the study in The Journal of Clinical Oncology

Relevant reading: The epidemiology of vitamin D and cancer incidence and mortality: A review (United States)

In-Depth [prospective case-control and  meta-analysis]:  In this prospective, population-based case-control study from the Scottish Managed Clinical Networks, 1598 patients who had stage I to III CRC were followed for a median of 8.9 years.  Patients were treated with curative surgery and chemotherapy.  546 patients had 25 hydroxy vitamin D levels less than 7.25 ng/mL, 528 patients had levels between 7.25 and 13.25 ng/mL, and 524 had levels greater than 13.25 ng/mL.  These groups were matched for factors known to influence CRC survival such as age, sex, and smoking status.  Serum vitamin D levels were measured postoperatively, ranging from 53 to 200 days, and were May-adjusted to correct for seasonal variations.  Patients with the highest vitamin D levels had a CRC-specific mortality HR of 0.68 (95% CI: 0.50-0.90) and an overall mortality HR of 0.70 (95% CI: 0.55-0.89) compared to those with the lowest levels.  In a meta-analysis of the present study’s data along with four previous studies, the adjusted HR for CRC-specific mortality was 0.67 (95% CI: 0.54-0.81) and 0.65 (95% CI: 0.55-0.77) for overall mortality.  A genetic haplotype analysis showed that the interaction between the GAGC haplotype and vitamin D level was significantly associated with overall survival (p=0.008).

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