Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Epidemiol Biomarkers Prev. 2021 Jan;30(1):203-209. doi: 10.1158/1055-9965.EPI-20-0351. Epub 2020 Sep 30.
Leukocyte telomere length (LTL) has been associated with risk of several cancers. The association between LTL and bladder cancer is still inconsistent.
In this large case-control study consisting of 2,011 patients with bladder cancer and 2,259 healthy controls of European ancestry, we investigated the associations of real-time qPCR-measured LTL (a retrospective case-control study) and genetically predicted LTL [a Mendelian randomization (MR) study] with bladder cancer risk. Genotypes from 10 LTL-associated SNPs were used as instrumental variables to predict LTL. We used an individual level data-based weighted genetic risk score (GRS) and a summary statistics-based inverse-variance weighting (IVW) method in MR analyses.
The qPCR-measured LTL was shorter in cases with muscle-invasive bladder cancer (MIBC) than those with non-muscle-invasive bladder cancer [NMIBC; ratio of telomere repeats copy number to single gene copy number (T/S): 1.19 ± 0.34 vs. 1.23 ± 0.36, = 0.081]. Multivariable logistic regression analyses showed long qPCR-measured LTL was associated with a reduced risk of MIBC. In MR analyses, genetically predicted LTL was weakly associated with bladder cancer risk in both the GRS analysis [OR = 1.13, per SD increase; 95% confidence interval (CI), 0.73-1.75; = 0.595] and the IVW analysis (OR = 1.14 per SD increase; 95% CI, 0.75-1.74; = 0.543).
There was no strong evidence supporting an association between LTL and bladder cancer risk in European Americans.
This is the largest study of LTL and bladder cancer risk. The study showed that LTL does not play an important role in bladder cancer etiology.
白细胞端粒长度（LTL）与多种癌症的风险相关。LTL 与膀胱癌之间的关联仍然不一致。
在这项由 2011 名膀胱癌患者和 2259 名欧洲血统健康对照组成的大型病例对照研究中，我们研究了实时 qPCR 测量的 LTL（回顾性病例对照研究）和遗传预测的 LTL [孟德尔随机化（MR）研究]与膀胱癌风险的关联。使用 10 个与 LTL 相关的 SNP 的基因型作为工具变量来预测 LTL。我们在 MR 分析中使用了个体水平数据加权遗传风险评分（GRS）和基于汇总统计信息的逆方差加权（IVW）方法。
qPCR 测量的 LTL 在肌层浸润性膀胱癌（MIBC）患者中比非肌层浸润性膀胱癌（NMIBC）患者短[端粒重复数与单基因拷贝数的比值（T/S）：1.19 ± 0.34 与 1.23 ± 0.36， = 0.081]。多变量逻辑回归分析表明，长 qPCR 测量的 LTL 与 MIBC 的风险降低相关。在 MR 分析中，遗传预测的 LTL 在 GRS 分析[OR = 1.13，每标准差增加；95%置信区间（CI），0.73-1.75； = 0.595]和 IVW 分析（OR = 1.14 每标准差增加；95%CI，0.75-1.74； = 0.543）中与膀胱癌风险均呈弱相关。
没有强有力的证据支持 LTL 与膀胱癌风险之间存在关联。
这是最大规模的 LTL 和膀胱癌风险研究。该研究表明，LTL 在膀胱癌发病机制中不起重要作用。
