and Variants of Vitamin D Receptor Gene Increase the Risk of Colorectal Cancer in a Saudi Population.

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 gene (, , and ) 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 values were determined with contingency table analysis following Hardy-Weinberg equilibrium equation.

Results: For the single-nucleotide polymorphism (SNP) (rs7975232), only the heterozygous (Aa) genotype increased the risk of CRC (OR = 3.4, RR = 2.3, and < 0.0001), whereas the SNP (rs731236) carriers with either the heterozygous (Tt) or homozygous (tt) genotype displayed an increased risk for the disease (OR = 6.18, RR = 4, < 0.0001; OR = 3, RR = 2.4, = 0.02, respectively). In contrast, heterozygous (Bb) and homozygous (bb) carriers of the SNP (rs1544410) had significantly lower risk for CRC ( < 0.0001). Finally, for the SNP (rs2228570), there was no association with CRC risk.

Conclusion: This study found that SNPs and increase the risk of CRC, whereas reduces the risk of CRC in the selected Saudi population. Therefore, and 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.