Dysregulation of vitamin D synthesis pathway genes in colorectal cancer: A case-control study

Background The cytochromes P450 are a superfamily of enzymes that control the synthesis of the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3. These enzymes contribute to the formation of 1,25-dihydroxyvitamin D3, which starts with a 25-hydroxylation byCYP2R1andCYP27A1and a subsequent 1 alpha-hydroxylation viaCYP27B1. Methods By using quantitative real-time polymerase chain reaction (qRT-PCR), we analyzed the expression ratio ofCYP2R1,CYP27A1andCYP27B1genes within the vitamin D metabolic pathway in a total of 75 colorectal cancer (CRC) tissues compared to the adjacent tissues. Furthermore, we evaluated the association ofCYP27B1rs4646536 andCYP2R1rs12794714 and rs10766196 polymorphisms with CRC risk in a total of 490 subjects, including 245 CRC patients and 245 non-cancer controls. The genotyping was performed using tetra-primer amplification refractory mutation system polymerase chain reaction (TP-ARMS-PCR) method. Results The results indicated 2.3 and 2.7 upregulation ofCYP2R1andCYP27B1genes in colorectal cancer tissues compared to the adjacent tissues, respectively. Rs12794714 AG genotype increased the risk of CRC (P = .03). Furthermore, a significant association was observed under the dominant inheritance model (P = .039). Conclusion CYP2R1andCYP27B1genes were over-expressed in CRC samples compared to the adjacent control tissues. Furthermore,CYP2R1rs12794714 variant was associated with the risk of CRC in the studied samples.CYP2R1rs10766196 andCYP27B1rs4646536 are not responsible forCYP2R1andCYP27B1genes expression alteration, respectively, butCYP2R1rs12794714 polymorphism may be the reason ofCYP2R1upregulation and increased the risk of CRC.