A Lack of Association between Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer: A Comprehensive...

Colorectal cancer (CRC) remains a major global health burden, and genetic factors such as vitamin D receptor (VDR) polymorphisms have been implicated in its pathogenesis. However, the translational relevance of these variants in clinical risk stratification remains unclear.

We conducted a comprehensive meta-analysis of case-control studies assessing the association between four common VDR single-nucleotide polymorphisms (Fok1, Apa1, Bsm1, and Taq1) and CRC risk, integrating data from PubMed, Embase, Google Scholar, and other sources through 2024. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under multiple genetic models. Heterogeneity, publication bias, and sensitivity analyses were performed. Statistical power was evaluated using G*Power 3.1.

Across 24 datasets from diverse ethnic populations, no significant associations were observed for any of the four VDR variants in allelic, dominant, recessive, or overdominant models. Statistical power exceeded 0.99 for all variants, indicating that the null results were unlikely due to sample size limitations.

This study provides robust evidence that these common VDR polymorphisms are not clinically functional as biomarkers for CRC susceptibility. Eliminating these variants from biomarker panels can help redirect resources toward more promising genetic or molecular predictors. These findings also reinforce the need for integrative studies exploring gene-environment interactions, particularly vitamin D status, diet, and lifestyle, to clarify the role of vitamin D pathways in CRC prevention and treatment.