Abstract
The deficiency of vitamin D has been reported to be relevant to cancer risk. DHCR7 and CYP2R1 are crucial components of vitamin D-metabolizing enzymes. Thus, accumulating researchers are concerned with the correlation between polymorphisms of DHCR7 and CYP2R1 genes and cancer susceptibility. Nevertheless, the conclusions of literatures are inconsistent. We conducted an integrated review for the correlation of DHCR7 and CYP2R1 SNPs with cancer susceptibility. In the meanwhile, a meta-analysis was performed using accessible data to clarify the association between DHCR7 and CYP2R1 SNPs and overall cancer risk. Literatures which meet the rigid inclusion and exclusion criteria were involved. The association of each SNP with cancer risk was calculated by odds ratios (ORs). 12 case-control designed studies covering 23780 cases and 27307 controls were ultimately evolved in the present meta-analysis of five SNPs (DHCR7 rs12785878 and rs1790349 SNP; CYP2R1 rs10741657, rs12794714, and rs2060793 SNP). We found that DHCR7 rs12785878 SNP was significantly related to cancer risk in the whole population, Caucasian subgroup, and hospital-based (HB) subgroup. DHCR7 rs1790349 SNP was analyzed to increase cancer risk in Caucasians. Moreover, CYP2R1 rs12794714-A allele had correlation with a lower risk of colorectal cancer. Our findings indicated that rs12785878, rs1790349, and rs12794714 SNPs might potentially be biomarkers for cancer susceptibility.
Highlights
Vitamin D, regarded as 1,25-dihydroxyvitamin D3, is a pivotal steroid prohormone which has a significant role to play in musculoskeletal health [1]
Genome-wide association studies (GWAS) have detected the correlations of 25-hydroxyvitamin D concentrations with single nucleotide polymorphisms (SNPs) on genes that participated in the vitamin D metabolic pathway [1, 16]
137 publications were gathered through database retrieval after removing duplicate hits. 125 articles were removed after browsing titles and abstracts: 21 were functional studies; 6 were review or meeting; 8 were not case-control studies; 17 were not related to DHCR7 or CYP2R1 SNPs; 53 were not concerned with carcinoma; and 13 were not correlated with carcinoma risk
Summary
Vitamin D, regarded as 1,25-dihydroxyvitamin D3, is a pivotal steroid prohormone which has a significant role to play in musculoskeletal health [1]. Studies have demonstrated that vitamin D level is highly heritable [16]. Genetic and epigenetic factors can impact several crucial steps along the metabolic pathway of vitamin D. Genes who directly participate in the vitamin D pathway gene are DHCR7, CYP2R1, VDR, CYP24A1, CYP27B1, and so on, and the aberrant expressions of them have been demonstrated to be associated with vitamin D concentrations and cancer [17,18,19,20,21]. Genome-wide association studies (GWAS) have detected the correlations of 25-hydroxyvitamin D concentrations with single nucleotide polymorphisms (SNPs) on genes that participated in the vitamin D metabolic pathway [1, 16]
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