U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population

Abstract

Telomeres play a critical role in biological ageing by maintaining chromosomal integrity and preventing chromosome ends fusion. Epidemiological studies have suggested that inter-individual differences of telomere length could affect predisposition to multiple cancers, but evidence regarding esophageal squamous cell carcinoma (ESCC) was still uncertain. Several telomere length-related single nucleotide polymorphisms (TL-SNPs) in Caucasians have been reported in genome-wide association studies. However, the effects of telomere length and TL-SNPs on ESCC development are unclear. Therefore, we conducted a case-control study (1045 ESCC cases and 1433 controls) to evaluate the associations between telomere length, TL-SNPs, and ESCC risk in Chinese population. As a result, ESCC cases showed overall shorter relative telomere length (RTL) (median: 1.34) than controls (median: 1.50, P<0.001). More interestingly, an evident nonlinear U-shaped association was observed between RTL and ESCC risk (P<0.001), with odds ratios (95% confidence interval) equal to 2.40 (1.84–3.14), 1.36 (1.03–1.79), 1.01 (0.76–1.35), and 1.37 (1.03–1.82) for individuals in the 1st (the shortest), 2nd, 3rd, and 5th (the longest) quintile, respectively, compared with those in the 4th quintile as reference group. No significant associations were observed between the eight reported TL-SNPs and ESCC susceptibility. These findings suggest that either short or extremely long telomeres may be risk factors for ESCC in the Chinese population.

Keywords

esophageal squamous cell carcinoma / telomere length / genetic variants / susceptibility / genome-wide association study

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Acknowledgements

This work was supported by grants from the Key Program of National Natural Science Foundation of China (No. 81230067); National Basic Research Program (973 Program, No. 2013CB910304); National Natural Science Foundation of China (Nos. 81422042, 81373090, and 81202267); Science Foundation for Distinguished Young Scholars in Jiangsu (No. BK20130042); Jiangsu Natural Science Foundation (Nos. BK2012443, BK2012841, and BK2012443); Doctoral Fund of Ministry of Education of China (No. 20123234120003); Jiangsu Province Clinical Science and Technology Projects (Clinical Research Center, No. BL2012008); and Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Compliance with ethics guidelines

Jiangbo Du, Wenjie Xue, Yong Ji, Xun Zhu, Yayun Gu, Meng Zhu, Cheng Wang, Yong Gao, Juncheng Dai, Hongxia Ma, Yue Jiang, Jiaping Chen, Zhibin Hu, Guangfu Jin, and Hongbing Shen declare no conflicts of interest. All procedures performed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

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