Lack of Associations between Vitamin D Metabolism-Related Gene Variants and Risk of Colorectal Cancer

Purpose: With regard to the protective effect of vitamin D against colorectal cancer (CRC), we evaluatedgenetic variants that might influence vitamin D metabolism: vitamin D receptor (VDR), vitamin D bindingprotein (GC), vitamin D 25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1).Materials and
Methods: A total of 657 subjects, including 303 cases with CRC and 354 controls were enrolled inthis case-control study. All 657 were genotyped for the four gene variants using PCR-RFLP methods.
Results:In this study, no significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1 (rs12794714),and CYP27B1 (rs3782130) gene variants in either genotype or allele frequencies between the cases with CRCand the controls and this lack of difference remained even after adjustment for age, BMI, sex, smoking status,NSAID use, and family history of CRC. Furthermore, no evidence for effect modification of the variants andCRC by BMI, sex, or tumor site was observed.
Conclusions: Our findings do not support a role for VDR, GC,and CYP27B1 genes in CRC risk in our Iranian population. Another interesting finding, which to our knowledgehas not been reported previously, was the lack of association with the CYP2R1 gene polymorphism. Nonetheless,our findings require confirmation and possible roles of vitamin D metabolism-related genes in carcinogenesisneed to be further investigated.