Genetic variants of Vitamin D receptor (VDR) gene could influence colorectal carcinogenesis. Numerous investigations, however, reported inconsistent results. Thus, we conducted a cumulative meta-analysis to clarify the controversy.
We performed a systematic search until May 2015 in Medline, Embase and Cochrane library databases. Dominant, recessive and additive genetic models were adopted to evaluate the effect of variant allele. We pooled the data using Mantel-Haenszel method and cumulative meta-analyses were carried out to observe the variation trend of the effect size.
A total of 44 studies were finally included. No significant association was detected between VDR variants and colorectal adenoma risk or recurrence.The BsmI variant homozygotes were found to be associated with significantly decreased risk of colorectal cancer (P = 0.02). The TaqI variant allele was observed to be associated with significantly increased risk of colon cancer in the subgroup analysis (P = 0.04). We also detected significant association between Cdx-2 variant and increased risk of colorectal cancer (P = 0.02); however, cumulative meta-analysis observed an unstable variation trend of odds ratio (OR) for that association. For survival of colorectal cancer patients, no significant association was found between these variants and overall or cancer-specific survival of colorectal cancer patients (Table).
Summary of meta-analysis results under additive model
|Risk||1.00 (0.94-1.06)||0.99 (0.93-1.05)|
|Recurrence||1.00 (0.93-1.07)||1.00 (0.89-1.12)|
|Risk||1.00 (0.92-1.09)||0.89 (0.80-0.99)*||1.02 (0.88-1.18)||1.10 (1.02-1.18)||1.00 (0.86-1.16)|
|Caucasian||1.04 (0.98-1.09)||0.86 (0.75-0.99)*||1.01 (0.85-1.20)||1.10 (1.02-1.18)||0.96 (0.81-1.14)|
|Asian||1.02 (0.70-1.47)||0.87 (0.36-2.13)*||1.03 [0.83-1.28]||1.13 (0.71-1.80)|
|Colonic||0.95 (0.80-1.13)||0.84 (0.72-0.98)*||1.20 [1.01-1.44]||1.30 (0.63-2.67)|
|Rectal||0.95 (0.83-1.08)||0.91 (0.75-1.11)*||0.97 (0.81-1.16)|
|Overall||0.95 (0.71-1.28)||0.89 (0.67-1.18)||1.16 (0.74-1.81)|
|Cancer- specific||0.98 (0.75-1.21)||1.18 (0.87-1.61)||0.79 (0.57-1.12)||1.02 (0.59-1.76)|
*Results of meta-analyses under recessive model
The Bsml variant is a protective factor for colorectal cancer risk, and the TaqI variant is a risk factor for colon cancer. The Cdx-2 variant might be associated with increased risk of colorectal cancer. Current evidence did not suggest that VDR variants could modify prognosis of colorectal cancer or adenoma. In the future, more well-designed studies exploring association between VDR variants on outcome of colorectal cancer or adenoma patients are expected to further confirm and extend our findings.
Clinical trial identification
All authors have declared no conflicts of interest.