Rajaraman Preetha, Wang Sophia S, Rothman Nathaniel, Brown Merideth M, Black Peter M, Fine Howard A, Loeffler Jay S, Selker Robert G, Shapiro William R, Chanock Stephen J, Inskip Peter D
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, EPS Room 7085, 6120 Executive Boulevard, Bethesda, MD 20892-7238, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1655-61. doi: 10.1158/1055-9965.EPI-07-0314.
Despite the potential importance of the cell cycle and apoptosis pathways in brain tumor etiology, little has been published regarding brain tumor risk associated with common gene variants in these pathways. Using data from a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n = 388), meningioma (n = 162), and acoustic neuroma (n = 73) with respect to 12 single nucleotide polymorphisms from 10 genes involved in apoptosis and cell cycle control: CASP8, CCND1, CCNH, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, PTEN, and TP53. We observed significantly decreased risk of meningioma with the CASP8 Ex14-271A>T variant [odds ratio (OR)(AT), 0.8; 95% confidence interval (95% CI), 0.5-1.2; OR(AA), 0.5; 95% CI, 0.3-0.9; P(trend) = 0.03] and increased risk of meningioma with the CASP8 Ex13+51G>C variant (OR(GC), 1.4; 95% CI, 0.9-2.1; OR(CC), 3.6; 95% CI, 1.0-13.1; P(trend) = 0.04). The CT haplotype of the two CASP8 polymorphisms was associated with significantly increased risk of meningioma (OR, 1.7; 95% CI, 1.1-2.6), but was not associated with risk of glioma or acoustic neuroma. The CCND1 Ex4-1G>A variant was associated with increased risk for glioma, and the Ex8+49T>C variant of CCNH was associated with increased risk of glioma and acoustic neuroma. The MDM2 Ex12+162A>G variant was associated with significantly reduced risk of glioma. Our results suggest that common variants in the CASP8, CCND1, CCNH, and MDM2 genes may influence brain tumor risk. Future research in this area should include more detailed coverage of genes in the apoptosis/cell cycle control pathways.
尽管细胞周期和凋亡途径在脑肿瘤病因学中具有潜在的重要性，但关于这些途径中常见基因变异与脑肿瘤风险的相关报道却很少。利用美国国立癌症研究所1994年至1998年进行的一项基于医院的病例对照研究的数据，我们评估了与凋亡和细胞周期控制相关的10个基因中的12个单核苷酸多态性与胶质瘤（n = 388）、脑膜瘤（n = 162）和听神经瘤（n = 73）风险的关系：CASP8、CCND1、CCNH、CDKN1A、CDKN2A、CHEK1、CHEK2、MDM2、PTEN和TP53。我们观察到，携带CASP8 Ex14 - 271A>T变异的个体患脑膜瘤的风险显著降低[比值比（OR）（AT），0.8；95%置信区间（95%CI），0.5 - 1.2；OR（AA），0.5；95%CI，0.3 - 0.9；趋势P值 = 0.03]，而携带CASP8 Ex13 + 51G>C变异的个体患脑膜瘤的风险增加（OR（GC），1.4；95%CI，0.9 - 2.1；OR（CC），3.6；95%CI，1.0 - 13.1；趋势P值 = 0.04）。CASP8两个多态性的CT单倍型与脑膜瘤风险显著增加相关（OR，1.7；95%CI，1.1 - 2.6），但与胶质瘤或听神经瘤风险无关。CCND1 Ex4 - 1G>A变异与胶质瘤风险增加相关，CCNH的Ex8 + 49T>C变异与胶质瘤和听神经瘤风险增加相关。MDM2 Ex12 + 162A>G变异与胶质瘤风险显著降低相关。我们的结果表明，CASP8、CCND1、CCNH和MDM2基因中的常见变异可能会影响脑肿瘤风险。该领域未来的研究应更详细地涵盖凋亡/细胞周期控制途径中的基因。
