Abstract
Abstract Backgrounds Telomeres are protective DNA-protein repeats structure at the extreme end of linear chromosomes that maintain chromosomal stability and integrity. Short telomere in peripheral blood leukocyte has been associated with an increased risk of multiple cancers. Moreover, heterogeneity of inter-individual telomere length is partly determined by hereditary factor. Recent genome-wide association studies (GWAS) have identified several telomere length related loci at 2p16.2 (ACYP2), 3q26 (TERC), 4q32.2 (NAF1), 5p15.33 (TERT), 10q24.33 (OBFC1), 19p12 (ZNF208) and 20q13.3 (RTEL1), some of which were also implicated with cancer risk. However, these findings were mainly observed in populations of European descent, and were not well demonstrated in other populations, especially for gastroesophageal cancer that is high incident in China but not in western countries. Design and Methods We measured relative telomere length (RTL) by quantitative real-time polymerase chain reaction in a Chinese case-control study including 1,136 gastric cancer cases, 1,045 esophageal cancer cases and 1,012 matched controls. Moreover, we performed genotyping by TaqMan assay for genetic variants at 2p16.2 (rs11125529), 3q26 (rs10936599), 4q32.2 (rs7675998), 5p15.33 (rs2736100, rs2736108), 10q24.33 (rs4387287), 19p12 (rs8105767), and 20q13.3 (rs755017). Results As compared with individuals in the fourth quintile of telomere length (i.e., moderately long telomeres), those with short telomeres were at an increased risk with ORs (95%CI) being 1.19 (0.92-1.55), 1.53 (1.19-1.98) and 3.00 (2.33-3.85) for the third, second and first quintiles, respectively. More interestingly, a significant elevated risk (OR= 1.54, 95%CI: 1.19-2.00) was also found in those at the fifth quintile with extreme long telomeres. We also confirmed that the G allele of rs2736100 at 5p15.33 exhibited a significant association with longer telomere length (r2= 0.106, P = 0.047), which, however, was not significantly associated with gastroesophageal cancer risk. We did not observe significant association of the other loci with telomere length or gastroesophageal cancer risk. Conclusions These findings suggest that either short or extreme long telomere may be risk factor for gastroesophageal cancer while telomere length related variants may be less important in the susceptibility to gastroesophageal cancer in Chinese population. Citation Format: Jiangbo Du, Xun Zhu, Chen Zhu, Hongxia Ma, Zhibin Hu, Hongbing Shen, Guangfu Jin. Telomere length, genetic variants and gastroesophageal cancer risk: a case-control study in Chinese population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-289. doi:10.1158/1538-7445.AM2014-LB-289
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