Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892-7238, USA.
Neuro Oncol. 2010 Jan;12(1):37-48. doi: 10.1093/neuonc/nop012. Epub 2009 Dec 10.
Although the etiology of primary brain tumors is largely unknown, prior studies suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma, but these tumors have not been well studied. We estimated the risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based, case-control study conducted by the National Cancer Institute. We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 (OR(CT/TT) = 3.5; 95% confidence interval: 1.8-6.9; P(trend) .0006), which persisted after controlling for multiple comparisons (P = .019). Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 (P(trend) .01); MUTYH rs3219466 (P(trend) .02), and PCNA rs25406 (P(trend) .03). The NBN rs1805794 minor allele variant was associated with decreased meningioma risk (P(trend) .006). Risk of acoustic neuroma was increased for the ERCC2 rs1799793 (P(trend) .03) and ERCC5 rs17655 (P(trend) .05) variants and decreased for the PARP1 rs1136410 (P(trend) .03). Decreased glioma risk was observed with the XRCC1 rs1799782 variant (P(trend) .04). Our results suggest that common DNA repair variants may affect the risk of adult brain tumors, especially meningioma.
虽然原发性脑肿瘤的病因在很大程度上尚不清楚,但先前的研究表明,DNA 修复多态性可能影响神经胶质瘤的风险。DNA 修复的改变也可能影响脑膜瘤和听神经瘤的风险,但这些肿瘤尚未得到充分研究。我们在国立癌症研究所进行的一项基于医院的病例对照研究中,评估了 362 例神经胶质瘤、134 例脑膜瘤和 69 例听神经瘤患者的风险,这些患者的非西班牙裔白人与 26 个基因中的 36 个单核苷酸多态性有关。我们观察到 GLTSCR1 rs1035938 的 T 变体与脑膜瘤风险显著增加(OR(CT/TT)=3.5;95%置信区间:1.8-6.9;P(trend).0006),并且在进行多次比较控制后仍然存在(P=.019)。ERCC4 rs1800067(P(trend).01)、MUTYH rs3219466(P(trend).02)和 PCNA rs25406(P(trend).03)的次要等位基因变异也观察到脑膜瘤风险显著增加。NBN rs1805794 次要等位基因变异与脑膜瘤风险降低相关(P(trend).006)。ERCC2 rs1799793(P(trend).03)和 ERCC5 rs17655(P(trend).05)的变体与听神经瘤风险增加相关,而 PARP1 rs1136410(P(trend).03)的变体与听神经瘤风险降低相关。XRCC1 rs1799782 变体与胶质瘤风险降低相关(P(trend).04)。我们的结果表明,常见的 DNA 修复变体可能会影响成人脑肿瘤的风险,尤其是脑膜瘤。