胶质母细胞瘤是原发性脑瘤中最常见和恶性程度最高的一种恶性肿瘤。我们的前期研究显示，经"全基因组范畴的关联研究" (Genome-wide association study, GWAS)发现的位于5p15.33区域TERT-CLPTM1L基因座位的rs2736100遗传多态与胶质母细胞瘤患者放疗后的总生存时间显著相关。本研究拟通过精细定位(fine-mapping)的方法，利用最新国际1000 Genomes、dbSNP和HapMap数据库信息，系统发掘经GWAS发现的胶质瘤相关5p15.33、7p11.2、8q24.21、9p21.3、11q23.3和20q13.33基因座位中的遗传多态与胶质母细胞瘤患者放疗后生存的相关关系，并进而阐明其生物学功能。在"后GWAS时代"，本项目将为GWAS研究结果的临床转化研究提供了一种新思路,并为实现针对患者不同遗传体质的个体化治疗打下基础。

Glioblastoma is the most common and most malignant primary brain tumor. Several genome-wide assocation study (GWAS) have identified a common TERT rs2736100 single nucleotide polymorphism (SNP) which was significantly associated with glioma risk in different ethnic populations. Interestingly, our previous studies demonstrated that the rs2736100 SNP locating at the chromosome 5p15.33 TERT locus was also significantly associated with overall survival of Chinese glioblastoma patients treated with radiotherapy. In the current sutdy, we would like to systematically investigate the association between genetic polymorphisms identified by glioma-GWAS at chromosome 5p15.33, 7p11.2, 8q24.21, 9p21.3, 11q23.3 and 20q13.33 loci and overall survival of glioblastoma patients reveiving irradiation through the fine-mapping approach with data form 1000 Genomes project, dbSNP database and HapMap project. Also, the biological role of these glioblastoma survival-related SNPs will be examined. In the post-GWAS era, our study will provide a new way for translation of GWAS results to clinical practices, and help laying foundation for personalized treatment for glioblastoma patients with different genetic background.

在本研究中，我们利用病例-对照研究的方法，以病理确诊的600例胶质瘤患者为病例，以具有性别和年龄匹配的600例健康个体为对照，揭示经GWAS研究确定的5p15.33、7p11.2、8q24.21、9p21.3、11q23.3和20q13.33基因座位单核苷酸多态与中国汉族人群胶质瘤发病风险的关系。研究发现，TERT基因作为的rs2853676单核苷酸多态与脑胶质瘤发病风险显著相关。与GG基因型相比，rs2853676 GA基因型携带者罹患脑胶质瘤的发病风险增加了0.54倍（95%置信区间：1.20-2.11；P =5.3×10-4）。类似的，rs2853676 AA基因型携带者罹患脑胶质瘤的发病风险增加了2.15倍（95%置信区间：1.95-5.17；P =1.5×10-4）。上述结果说明，TERT基因作为的rs2853676单核苷酸多态为各个人群共同的脑胶质瘤发病风险遗传变异。