维生素D受体基因变异增加沙特人群患结直肠癌的风险。
and Variants of Vitamin D Receptor Gene Increase the Risk of Colorectal Cancer in a Saudi Population.
作者信息
Al-Ghafari Ayat B, Balamash Khadijah S, Al Doghaither Huda A
机构信息
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
出版信息
Saudi J Med Med Sci. 2020 Sep-Dec;8(3):188-195. doi: 10.4103/sjmms.sjmms_357_19. Epub 2020 Aug 20.
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.
背景
编码维生素D受体（VDR）的基因多态性会影响维生素D对包括结直肠癌（CRC）在内的多种癌症的保护作用。
目的
本研究旨在评估该基因的四种主要多态性（ 、 、 和 ）对沙特人群患结直肠癌风险的影响。
材料与方法
这项病例对照研究于2017年9月至2018年8月期间，从阿卜杜勒阿齐兹国王大学医院的肿瘤诊所招募了132例结直肠癌患者，并从沙特阿拉伯吉达法赫德国王总医院血库招募了124名健康对照。所有参与者均为沙特人，年龄在20 - 80岁之间。从外周血细胞中提取基因组DNA样本，并通过聚合酶链反应进行扩增。使用限制性片段长度多态性技术，用不同的内切酶消化所得片段以揭示基因型。根据哈迪 - 温伯格平衡方程，通过列联表分析确定基因型分布、等位基因频率、优势比（OR）、风险比（RR）和 值。
结果
对于 单核苷酸多态性（SNP）（rs7975232），只有杂合子（Aa）基因型会增加患结直肠癌的风险（OR = 3.4，RR = 2.3，且 < 0.0001），而 SNP（rs731236）的杂合子（Tt）或纯合子（tt）基因型携带者患该疾病的风险增加（OR = 6.18，RR = 4， < 0.0001；OR = 3，RR = 2.4， = 0.02，分别）。相比之下， SNP（rs1544410）的杂合子（Bb）和纯合子（bb）携带者患结直肠癌的风险显著降低（ < 0.0001）。最后，对于 SNP（rs2228570），与结直肠癌风险无关。
结论
本研究发现，在选定的沙特人群中， SNP和 会增加患结直肠癌的风险，而 会降低患结直肠癌的风险。因此， 和 SNP有可能用作结直肠癌的诊断生物标志物。然而，这些变体增加或降低结直肠癌风险的分子机制有待研究。
Zotero 插件