Sun Yuhui, Tao Wade, Huang Maosheng, Wu Xifeng, Gu Jian
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Cell Mol Med. 2017 Mar;21(3):510-518. doi: 10.1111/jcmm.12995. Epub 2016 Nov 7.
Most ovarian cancer patients present at an advanced stage with poor prognosis. Telomeres play a critical role in protecting chromosomes stability. The associations of genetic variants in telomere maintenance genes and ovarian cancer risk and outcome are unclear. We genotyped 137 single nucleotide polymorphisms (SNPs) in telomere-maintenance genes in 417 ovarian cancer cases and 417 matched healthy controls to evaluate their associations with cancer risk, survival and therapeutic response. False discovery rate Q-value was calculated to account for multiple testing. Eleven SNPs from two genes showed nominally significant associations with the risks of ovarian cancer. The most significant SNP was TEP1: rs2228026 with participants carrying at least one variant allele exhibiting a 3.28-fold (95% CI: 1.72-6.29; P < 0.001, Q = 0.028) increased ovarian cancer risk, which remained significant after multiple testing adjusting. There was also suggested evidence for the associations of SNPs with outcome, although none of the associations had a Q < 0.05. Seven SNPs from two genes showed associations with ovarian cancer survival (P < 0.05). The strongest association was found in TNKS gene (rs10093972, hazard ratio = 1.88; 95% CI: 1.20-2.92; P = 0.006, Q = 0.076). Five SNPs from four genes showed suggestive associations with therapeutic response (P < 0.05). In a survival tree analysis, TEP1:rs10143407 was the primary factor contributing to overall survival. Unfavourable genotype analysis showed a cumulative effect of significant SNPs on ovarian cancer risk, survival and therapeutic response. Genetic variations in telomere-maintenance genes may be associated with ovarian cancer risk and outcome.
大多数卵巢癌患者就诊时已处于晚期，预后较差。端粒在保护染色体稳定性方面起着关键作用。端粒维持基因中的遗传变异与卵巢癌风险及预后之间的关联尚不清楚。我们对417例卵巢癌病例和417例匹配的健康对照者的端粒维持基因中的137个单核苷酸多态性（SNP）进行基因分型，以评估它们与癌症风险、生存率和治疗反应的关联。计算错误发现率Q值以考虑多重检验。来自两个基因的11个SNP与卵巢癌风险显示出名义上的显著关联。最显著的SNP是TEP1：rs2228026，携带至少一个变异等位基因的参与者患卵巢癌的风险增加3.28倍（95%可信区间：1.72 - 6.29；P < 0.001，Q = 0.028），在多重检验校正后仍具有显著性。也有证据表明SNP与预后有关联，尽管没有一个关联的Q < 0.05。来自两个基因的7个SNP与卵巢癌生存率有关联（P < 0.05）。在TNKS基因中发现了最强的关联（rs10093972，风险比 = 1.88；95%可信区间：1.20 - 2.92；P = 0.006，Q = 0.076）。来自四个基因的5个SNP与治疗反应显示出提示性关联（P < 0.05）。在生存树分析中，TEP1：rs10143407是影响总生存的主要因素。不利基因型分析显示显著SNP对卵巢癌风险、生存率和治疗反应具有累积效应。端粒维持基因中的遗传变异可能与卵巢癌风险及预后有关。
