Department of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, PR China.
Cancer Epidemiol. 2012 Dec;36(6):525-7. doi: 10.1016/j.canep.2012.06.008. Epub 2012 Jul 12.
Current evidence suggests that a majority of the inherited risks play a major role in glioma susceptibility, and glioma is due to the co-inheritance of multiple low-risk variants. These variants can be identified through association studies including such as genome-wide association studies (GWAS), which has led the glioma epidemiology researchers to focus on identifying potential disease-causing factors.
We evaluated and validated 10 tag single nucleotide polymorphisms (tSNPs) in seven genes associated with glioma susceptibility in a Han Chinese population, including 301 glioma cases and 302 controls, using a multiplexed single nucleotide polymorphism (SNP) MassEXTEND assay. We ascertained the genotypic frequencies for each tSNP in control subjects were within Hardy-Weinberg equilibrium (HWE) using an exact test, and then compared the genotype and allele frequencies of glioma patients and control subjects using the χ2 test. We then applied three genetic models (dominant, recessive, and additive) using PLINK software to assess the association of each tSNP with glioma risk.
We identified two tSNPs to be associated with glioma susceptibility (rs1695, GSTP1, P = 0.019; rs2853676, TERT, P = 0.039), which we confirmed using dominant and additive model analyses. The genotype “GA” for rs1695 was recognized to be a protective genotype for glioma (OR, 0.67; 95% CI, 0.47-0.96; P = 0.027), while the genotype “AG” for rs2853676 was shown to be a risk genotype for glioma (OR, 1.50; 95% CI, 1.05-2.15; P = 0.025).
Our results, and those from previous studies, suggest potential genetic contributes for GSTP1 and TERT in glioma development.
目前的证据表明，大多数遗传风险在胶质母细胞瘤易感性中起主要作用，并且胶质母细胞瘤是由于多种低风险变体的共同遗传所致。这些变体可以通过关联研究（包括全基因组关联研究（GWAS））来识别，这使得胶质母细胞瘤流行病学研究人员专注于确定潜在的致病因素。
我们使用多重单核苷酸多态性（SNP）MassEXTEND 检测，在汉族人群中评估和验证了与胶质母细胞瘤易感性相关的七个基因中的 10 个标签单核苷酸多态性（tSNP），包括 301 例胶质母细胞瘤病例和 302 例对照。我们使用精确检验确定对照受试者中每个 tSNP 的基因型频率是否处于哈迪-温伯格平衡（HWE），然后使用 χ2 检验比较胶质母细胞瘤患者和对照受试者的基因型和等位基因频率。然后，我们使用 PLINK 软件应用三种遗传模型（显性、隐性和加性）来评估每个 tSNP 与胶质母细胞瘤风险的关联。
我们发现两个 tSNP 与胶质母细胞瘤易感性相关（rs1695，GSTP1，P = 0.019；rs2853676，TERT，P = 0.039），我们通过显性和加性模型分析证实了这一点。rs1695 的基因型“GA”被认为是胶质母细胞瘤的保护性基因型（OR，0.67；95%CI，0.47-0.96；P = 0.027），而 rs2853676 的基因型“AG”则显示为胶质母细胞瘤的风险基因型（OR，1.50；95%CI，1.05-2.15；P = 0.025）。
我们的结果以及之前的研究结果表明，GSTP1 和 TERT 在胶质母细胞瘤发生中具有潜在的遗传贡献。
