Genetic variants affecting telomere length are associated with the prognosis of esophageal squamous cell carcinoma in a Chinese population

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• 作者：Yue Lu ; Caiwang Yan ; Jiangbo Du ; Yong Ji ; Yong Gao ; Xun Zhu ; Fei Yu ; Tongtong Huang ; Juncheng Dai ; Hongxia Ma ; Yue Jiang ; Jiaping Chen ; Hongbing Shen ; Guangfu Jin ; Yongmei Yin and Zhibin Hu
• 刊名：Molecular Carcinogenesis
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：56
• 期：3
• 页码：1021-1029
• 全文大小：132K
• ISSN：1098-2744

文摘

Telomeres are essential for maintaining chromosomal stability and are crucial in tumor progression. Previous studies have explored the associations between telomere length and cancer prognosis, but the findings are inconclusive. Genome-wide association studies have identified several genetic variants associated with telomere length in Caucasians. However, the roles of telomere length and related genetic variants on esophageal squamous cell carcinoma (ESCC) prognosis are largely unknown. Therefore, we conducted a case-cohort study with 431 ESCC patients to assess the associations between relative telomere length (RTL), eight known telomere length related variants and the overall survival of ESCC in Chinese population. We found that as compared with the reference group, patients in the fifth (the longest) quintile had a significantly better prognosis [(adjusted hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.34–0.98, P = 0.041]. Furthermore, A allele of rs2736108 was significantly associated with both the increased RTL (P = 0.048) and the better prognosis of ESCC (adjusted HR = 0.55, 95%CI = 0.38–0.79, P = 1.31 × 10p>−3p>). Mediation analysis indicated that the effect of rs2736108 on ESCC prognosis was partly explained by RTL (1.99%). Stepwise Cox proportional hazard analysis suggested that rs2736108 played an important protective role in ESCC prognosis (HR = 0.57, 95%CI = 0.40–0.81, P = 1.97 × 10p>−p>p>3p>). Our findings provide evidence that prolonged telomere length is a protective factor for ESCC patients’ survival and the known telomere length related genetic variant rs2736108 can contribute to the prognosis of ESCC as well in Chinese population.