Department of Biochemistry, Government Medical College Srinagar and Associated SMHS and Superspeciality Hospital and Research Centre, University of Kashmir, Srinagar, J&K, 190010, India.
Department of Surgery, Government Medical College Srinagar and Associated SMHS and Superspeciality Hospital, Srinagar, J&K, 190010, India.
Mol Biol Rep. 2021 Apr;48(4):3313-3325. doi: 10.1007/s11033-021-06376-z. Epub 2021 May 3.
Vitamin D receptor (VDR) mediates cellular processes like cell cycle arrest and apoptosis which effect cancer susceptibility. VDR single nucleotide polymorphisms (SNPs) have a significant influence on functioning of VDR protein and subsequently contribute to the risk of cancer occurrence and progression. The present case-control study was carried out between 2016 and 2020 to investigate the association of VDR BsmI/ApaITaqI SNPs with Gastric Cancer (GC) risk in ethnic Kashmiri population not only for establishing a molecular marker for GC but also to facilitate the outcomes of personalized medicine in future. The polymorphisms of BsmI and ApaI of the VDR gene were evaluated using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism followed by Di-Deoxy Sanger sequencing in 143 GC cases and 150 controls. The mean age (in years) was 53.5 ± 7.92 and 51.2 ± 8.25 and mean Body mass index was 22.68 ± 4.27 kg/m and 23.81 ± 3.71 kg/m for cases and controls respectively. The mean CEA levels of GC cases was 40.2 ± 10.9 ng/ml. Genotypic distribution of VDR BsmI differed significantly between GC cases and controls (GG vs GA + AA; adjusted P = 0.014) and followed dominant mode of inheritence. Stratification of VDR BsmI revealed that frequency of variant genotype (GA + AA) was significantly higher in Preobese GC cases (P = 0.001), GC patients consuming < 5 cups of salt tea/day (P < 0.0001) and with no family history of gastrointestinal cancer (P = 0.014) compared to healthy controls. ATC haplotype associated with high GC risk. In conclusion, our study suggests that VDR BsmI SNP has a significant association with increased risk of GC especially in preobese population and BsmI/ApaITaqI SNPs significantly decreased the overall survival in GC patients of Kashmiri population.
维生素 D 受体 (VDR) 介导细胞周期停滞和细胞凋亡等细胞过程，从而影响癌症易感性。VDR 单核苷酸多态性 (SNP) 对 VDR 蛋白的功能有显著影响，进而增加癌症发生和进展的风险。本病例对照研究于 2016 年至 2020 年进行，旨在研究 VDR BsmI/ApaITaqI SNP 与克什米尔族群中胃癌 (GC) 风险的关联，不仅为 GC 建立分子标志物，而且为未来的个性化医学提供结果。使用聚合酶链反应-限制性片段长度多态性 (PCR-RFLP) 评估 VDR 基因的 BsmI 和 ApaI 多态性，随后进行 Di-Deoxy Sanger 测序，共纳入 143 例 GC 病例和 150 例对照。病例和对照的平均年龄 (岁) 分别为 53.5±7.92 和 51.2±8.25，平均体重指数 (kg/m) 分别为 22.68±4.27 和 23.81±3.71。GC 病例的平均 CEA 水平为 40.2±10.9ng/ml。VDR BsmI 的基因型分布在 GC 病例和对照组之间有显著差异 (GG 与 GA+AA；调整后的 P=0.014)，并遵循显性遗传模式。VDR BsmI 分层显示，在肥胖前 GC 病例中，变异基因型 (GA+AA) 的频率显著更高 (P=0.001)，每天饮用<5 杯盐茶的 GC 患者 (P<0.0001) 以及无胃肠道癌症家族史的患者 (P=0.014) 与健康对照组相比。ATC 单倍型与高 GC 风险相关。总之，本研究表明，VDR BsmI SNP 与 GC 风险增加显著相关，尤其是在肥胖前人群中，BsmI/ApaITaqI SNP 显著降低了克什米尔族群 GC 患者的总生存率。
