Department of Clinical Oncology, University of Hong Kong, Hong Kong (Special Administrative Region), People's Republic of China.
Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong (Special Administrative Region), People's Republic of China.
Int J Cancer. 2018 Nov 1;143(9):2289-2298. doi: 10.1002/ijc.31617. Epub 2018 Aug 7.
Telomere shortening occurs as an early event in tumorigenesis. The TERT-CLPTM1L locus associates with nasopharyngeal carcinoma (NPC) risk. It remains unknown if leukocyte telomere length (LTL) associates with NPC risk and survival. The relative LTL (rLTL) was measured by quantitative-PCR in 2,996 individuals comprised of 1,284 NPC cases and 1712 matched controls. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression. The hazard ratio (HR) and 95% CI were calculated by Cox regression for survival analysis with rLTL and other clinical parameters in 1,243 NPC with a minimum follow-up period of 25 months. NPC patients had significantly shorter telomere length than controls. Shorter rLTL significantly associated with increased NPC risk, when the individuals were dichotomized into long and short telomeres based on median-split rLTL in the control group (OR = 2.317; 95% CI = 1.989-2.700, p = 4.10 × 10 ). We observed a significant dose-response association (p = 3.26 × 10 ) between rLTL and NPC risk with OR being 3.555 (95% CI = 2.853-4.429) for the individuals in the first quartile (shortest) compared with normal individuals in the fourth quartile (longest). A multivariate Cox regression analysis adjusted by age demonstrated an independent effect of rLTL on NPC survival for late-stage NPC patients, when the individuals were categorized into suboptimal rLTL versus the medium rLTL based on a threshold set from normal (HR = 1.471, 95% CI = 1.056-2.048, p = 0.022). Shorter blood telomeres may be markers for higher susceptibility for NPC risk. Suboptimal rLTL may be a poor prognostic factor for advanced NPC patients, as it associates independently with poor survival.
端粒缩短是肿瘤发生的早期事件。TERT-CLPTM1L 基因座与鼻咽癌（NPC）风险相关。白细胞端粒长度（LTL）是否与 NPC 风险和生存相关尚不清楚。在 2996 名个体中，通过定量 PCR 测量相对 LTL（rLTL），其中包括 1284 例 NPC 病例和 1712 名匹配对照。通过 logistic 回归计算比值比（OR）和 95%置信区间（CI）。在 1243 例 NPC 患者中，使用 Cox 回归进行生存分析，在最短随访时间为 25 个月时，rLTL 和其他临床参数的风险比（HR）和 95%CI。NPC 患者的端粒长度明显短于对照组。根据对照组 rLTL 的中位数分割，将个体分为长端粒和短端粒时，较短的 rLTL 与 NPC 风险显著相关（OR=2.317；95%CI=1.989-2.700，p=4.10×10）。我们观察到 rLTL 与 NPC 风险之间存在显著的剂量反应关系（p=3.26×10），与第四四分位（最长）的正常个体相比，第一四分位（最短）个体的 OR 为 3.555（95%CI=2.853-4.429）。当个体根据正常个体设定的阈值分为 rLTL 不充分与中等 rLTL 时，调整年龄的多变量 Cox 回归分析显示 rLTL 对晚期 NPC 患者的 NPC 生存有独立影响（HR=1.471，95%CI=1.056-2.048，p=0.022）。较短的血液端粒可能是 NPC 风险易感性较高的标志物。rLTL 不充分可能是晚期 NPC 患者不良预后的因素，因为它与不良生存独立相关。
