Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Neuro Oncol. 2013 Aug;15(8):1041-7. doi: 10.1093/neuonc/not051. Epub 2013 Jun 3.
Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma.
SNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between "number of risk alleles" and "age at diagnosis," adjusted for sex and study site and stratified by tumor grade/histology where appropriate.
Four SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10(-22) and P = 9.5 × 10(-7), respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10(-4) and P = 2.5 × 10(-4), respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups.
Carrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres).
全基因组关联研究表明，7 个基因中的单核苷酸多态性（SNP）与胶质瘤风险因素有关，其中 2 个（TERT、RTEL1）与端粒酶结构/功能有关。我们研究了这些已确定的胶质瘤风险位点与胶质瘤患者诊断时年龄之间的关系。
来自加利福尼亚大学旧金山分校（n = 1434）和梅奥诊所（n = 852）的 2286 名白种人胶质瘤患者提供了 SNP 基因型数据。进行回归分析以检验“风险等位基因数”与“诊断时年龄”之间的关系，调整性别和研究地点，并根据肿瘤分级/组织学进行分层，在适当情况下。
有 4 个 SNP 与诊断时年龄显著相关。携带更多 rs55705857（CCDC26）和 rs498872（PHLDB1）的风险等位基因与更年轻的诊断年龄相关（P = 1.4×10(-22)和 P = 9.5×10(-7)）。这些 SNP 是少突胶质细胞瘤更强的危险因素，少突胶质细胞瘤往往发生在年轻患者中，它们与诊断时年龄的关系因肿瘤亚型而异。相比之下，携带更多 rs2736100（TERT）和 rs6010620（RTEL1）的风险等位基因与较晚的诊断年龄相关（P = 6.2×10(-4)和 P = 2.5×10(-4)）。这些 SNP 是所有胶质瘤分级/组织学的危险因素，它们与诊断时年龄的关系在肿瘤亚组中是一致的。
携带更多的风险等位基因可能会降低诊断时的年龄。然而，端粒酶相关基因变异所带来的胶质瘤易感性并不遵循这一模式。这支持了这样一种假设，即与端粒酶相关的端粒维持机制与生命后期发生的胶质瘤更为相关，而与端粒酶无关的机制（即端粒的替代延长）则不然。
