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Background: Cancers may arise from cells with dysregulated telomeric functions due to shorten telomere length. We and others previously found that short leukocyte telomere length was associated with markedly evaluated risk of esophageal squamous cell carcinoma (ESCC). Hence, we hypothesized that single nucleotide polymorphisms (SNPs) associated with shorter telomere length may contribute to ESCC predisposition. Methods: We systematically evaluated association between seven candidate seven SNPs ( CXCR4 rs6430612, TERT rs13172201, TERT rs10069690, TERT rs2853676, TERT rs451360, OBFC1 rs4387287, and VPS34 rs2162440) and ESCC risk in two case-control sets consisting of 1588 ESCC cases and 1600 controls. Logistic regression models were utilized to estimate associations between SNPs and ESCC susceptibility and odds ratios (ORs) and their 95% confidence intervals (95% CIs) were computed. Results: We firstly identified three SNPs (rs6430612, rs13172201 and rs4387287) which are significantly associated with telomere length in Chinese populations (all P &lt;0.05). Importantly, CXCR4 rs6430612 and OBFC1 rs4387287 polymorphisms significantly confer reduced risk of ESCC ( P =1.7×10 -7 and P =3.9×10 -5 ). On the contrary, we observed an evidently increased risk for ESCC development associated with TERT rs13172201 genetic variant ( P =2.2×10 -4 ). Conclusions: In summary, rs6430612, rs13172201 and rs4387287 might be key genetic components in complicated regulation of telomere length and contributing to ESCC predisposition. Our results elucidate the prevalent involvement of genetic variants in telomere biology and further provide pathogenic insights into the role of telomeres in cancer development.

Identification of Leukocyte telomere length-related genetic variants contributing to predisposition of Esophageal Squamous Cell Carcinoma