Walsh Kyle M, Codd Veryan, Smirnov Ivan V, Rice Terri, Decker Paul A, Hansen Helen M, Kollmeyer Thomas, Kosel Matthew L, Molinaro Annette M, McCoy Lucie S, Bracci Paige M, Cabriga Belinda S, Pekmezci Melike, Zheng Shichun, Wiemels Joseph L, Pico Alexander R, Tihan Tarik, Berger Mitchell S, Chang Susan M, Prados Michael D, Lachance Daniel H, O'Neill Brian Patrick, Sicotte Hugues, Eckel-Passow Jeanette E, van der Harst Pim, Wiencke John K, Samani Nilesh J, Jenkins Robert B, Wrensch Margaret R
1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
1] Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Nat Genet. 2014 Jul;46(7):731-5. doi: 10.1038/ng.3004. Epub 2014 Jun 8.
Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined = 8.3 × 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma and replication data (1,644 cases and 7,736 controls). This region has previously been associated with mean leukocyte telomere length (LTL). We therefore examined the relationship between LTL and both this new risk locus and other previously established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684 individuals). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 × 10(-20) and 4.4 × 10(-19), respectively). In contrast, risk-associated alleles near RTEL1 were inconsistently associated with LTL, suggesting the presence of distinct causal alleles. No other risk loci for glioma were associated with LTL. The identification of risk alleles for glioma near TERC and TERT that also associate with telomere length implicates telomerase in gliomagenesis.
胶质瘤是成人中最常见的中枢神经系统癌症，预后较差。在此，我们鉴定出一个与胶质瘤风险相关的新单核苷酸多态性（SNP），即rs1920116（靠近端粒酶RNA组分（TERC）），在一项高级别胶质瘤全基因组关联研究（GWAS）和复制数据（1644例病例和7736例对照）的荟萃分析中达到全基因组显著性水平（P合并 = 8.3 × 10^(-9)）。该区域先前已与平均白细胞端粒长度（LTL）相关联。因此，我们使用来自最近一项LTL全基因组关联研究（n = 37684名个体）的数据，研究了LTL与这个新的风险位点以及其他先前确定的胶质瘤风险位点之间的关系。TERC和端粒酶逆转录酶（TERT）附近与胶质瘤风险相关的等位基因与更长的LTL强烈相关（P分别为5.5 × 10^(-20)和4.4 × 10^(-19)）。相比之下，RTEL1附近的风险相关等位基因与LTL的关联不一致，表明存在不同的因果等位基因。没有其他胶质瘤风险位点与LTL相关。TERC和TERT附近与胶质瘤风险相关的等位基因也与端粒长度相关，这表明端粒酶在胶质瘤发生中起作用。
