TaqI and ApaI variants of Vitamin D receptor gene increase the risk of colorectal cancer in a Saudi population

Abstract

Background: Polymorphisms in the gene encoding the vitamin D receptor (VDR) affect the protective role of vitamin D against many types of cancers, including colorectal cancer (CRC). Objective: The objective of this study was to assess the effect of four major polymorphisms of the VDR gene ( ApaI , TaqI , BsmI and FokI ) on the risk of CRC in a Saudi population. Materials and Methods: This case–control study recruited 132 CRC patients from the oncology clinics at King Abdulaziz University Hospital and 124 healthy controls from the blood bank at King Fahad General Hospital, Jeddah, Saudi Arabia, between September 2017 and August 2018. All participants were Saudis and aged 20–80 years. Genomic DNA samples were extracted from the peripheral blood cells and amplified with polymerase chain reaction. The resulting fragments were digested with different endonucleases to reveal the genotypes using the restriction fragment length polymorphism technique. The genotype distribution and allele frequency, odds ratio (OR), risk ratio (RR) and P values were determined with contingency table analysis following Hardy–Weinberg equilibrium equation. Results: For the ApaI single-nucleotide polymorphism (SNP) (rs7975232), only the heterozygous (Aa) genotype increased the risk of CRC (OR = 3.4, RR = 2.3, and P < 0.0001), whereas the TaqI SNP (rs731236) carriers with either the heterozygous (Tt) or homozygous (tt) genotype displayed an increased risk for the disease (OR = 6.18, RR = 4, P < 0.0001; OR = 3, RR = 2.4, P = 0.02, respectively). In contrast, heterozygous (Bb) and homozygous (bb) carriers of the BsmI SNP (rs1544410) had significantly lower risk for CRC ( P < 0.0001). Finally, for the FokI SNP (rs2228570), there was no association with CRC risk. Conclusion: This study found that VDR SNPs ApaI and TaqI increase the risk of CRC, whereas BsmI reduces the risk of CRC in the selected Saudi population. Therefore, ApaI and TaqI SNPs could potentially be used as a diagnostic biomarker for CRC. However, the molecular mechanisms by which these variants increase or decrease the risk of CRC need to be investigated.

Association of vitamin D receptor polymorphisms with colorectal cancer susceptibility: A systematic meta-analysis

“…It has been proposed that high VDR expression could be a good prognostic marker for CRC. [ 72 ] In our meta-analysis, 9 studies on BsmI polymorphism, 2 studies on FokI polymorphism, [ 39 , 41 ] 5 studies on TaqI polymorphism, [ 23 , 29 , 37 , 47 , 64 ] and 5 studies on ApaI polymorphism [ 46 , 47 , 49 , 54 , 55 ] were deviated from HWE, respectively. A total of 47 reports predicted a possible genetic association, and 45 of which were used to comprehensively estimate the relationship between VDR polymorphisms (FokI, BsmI, TaqI, ApaI, Cdx-2, and Tru9I) and CRC risk.…”

“…Zhang et al [ 22 ] found no association between FokI, BsmI, ApaI, TaqI, and CRC risk; however, there was a significant interaction between dietary vitamin D intake and ApaI polymorphisms in relation to CRC risk. Al-Ghafari et al [ 23 ] demonstrated that the ApaI and TaqI polymorphisms were associated with increased CRC risk and that the BsmI polymorphism was related to decreased CRC risk in the Saudi population. VDR polymorphic sites, including FokI, BsmI, ApaI, TaqI, Tru9I, and Cdx2, have been evaluated in genetic association studies on CRC.…”

Vitamin D Receptor Gene Polymorphisms and the Risk of CIN2+ in Shanxi Population

“…(10) The parameters of Bio-TekEPOCH2 microplate reader were set at 450 nm and. (11) The standard curve equation was calculated to obtain the sample concentrations.…”

“…VDR belongs to the nuclear receptor family with a typical nuclear receptor domain, including DNA-binding domain, a hinge region, a ligand-binding domain, and a carboxy-terminal activation function 2 domain that interacts with coregulators [ 10 ]. The VDR gene is located on chromosome 12q12-14, which contains two promoters and 8 exons [ 11 ]. So far, more than 60 VDR single nucleotide polymorphisms (single-nucleotide polymorphisms, SNPs) have been identified, but the most studied are FOKI (exon 2), BsmI, ApaI (intron 8), and TaqI (exon 9).…”

“…So far, more than 60 VDR single nucleotide polymorphisms (single-nucleotide polymorphisms, SNPs) have been identified, but the most studied are FOKI (exon 2), BsmI, ApaI (intron 8), and TaqI (exon 9). The four SNP are located in different regions of the VDR gene and are potentially linked to many diseases [ 11 , 12 ]. Many studies have analyzed the association of VDR SNP with cancer, such as breast cancer (FokI, BsmI, and ApaI), prostate cancer (FokI, BsmI, and TaqI), colorectal cancer (FokI, BsmI, and TaqI), and skin cancer (FokI, BsmI, and TaqI) [ 13 ], but there are still controversies.…”