Vitamin D receptor gene variations and their haplotypic association: Possible impact on gastric cancer risk.

Abstract

Vitamin D receptor (VDR) gene alterations have been associated with the occurrence and prognosis of various types of cancers, but only few studies have focussed on gastric cancer (GC) risk. This case-control study was conceived to evaluate possible association of VDR polymorphisms (Fok1, Taq1, and Cdx2) with GC risk. A total of 293 subjects, including 143 GC patients and 150 controls were included in this study. The genotypes were elucidated by polymerase chain reaction-restriction fragment length polymorphism followed by DNA sequencing. The frequency of Fok1 genotypes (TC and TT) was found higher in GC cases compared to controls (P ≤ 0.05). In the stratified analysis, we observed a significant association of the (CT + TT) variant with GC risk in males, rural dwellers, smokers, and preobese cases, and those having no family history of Gastrointestinal cancer (P ≤ 0.05). In silico analysis predicted that the Fok1 variant impacts the stability and functional efficiency of the protein. Some exact haplotypes (CCG and CCA) of the VDR gene may act as low penetrance alleles in inclination to GC. VDR Fok1 polymorphism is significantly associated with GC risk in the Kashmiri population. Specific haplotypes in the VDR gene could act synergistically in the development of GC.