Constitutive short chromosome-specific telomere length of 17p and 12q, but not XpYp, 11q and 2p is associated with increased esophageal cancer risk

A10

Telomere length plays a very critical role in the maintenance of genome integrity. The shortening of telomeres may cause genetic instability and thus promote cancer development. Previous studies mainly shaded light on the overall telomere shortening. However, the association between the chromosome-specific telomere shortening and tumorigenesis of a certain type of cancer has yet to be established. Therefore, in the present study, we measured both the overall telomere length and individual telomere lengths of XpYp, 17p,2p, 11q and 12q with quantitative real-time PCR in peripheral blood lymphocytes (PBLs) from an esophageal cancer case-control study consisting of 92 cases and 92 controls matched on age (±1 year), gender and ethnicity. The results showed that, compared with matched controls, EC patients had significantly shorter overall telomere length [case vs. control (mean ± standard deviation): 1.19±0.39 vs. 1.36±0.42; p=0.001] and individual telomere lengths of 17p (case vs. control: 1.08±0.27 vs. 1.23±0.38; p=0.018) and 12 q (case vs. control: 1.44±0.99 vs. 2.14±2.08; p=0.008). No significant differences of the individual telomere length were observed between cases and controls for chromosome XpYp (case vs. control: 0.91±0.31 vs. 0.85±0.23; p=0.08), 2p (case vs. control: 1.20±0.58 vs. 1.20±0.54; p=0.988) and 11q (case vs. control: 0.77±0.83 vs. 0.75±0.68; p=0.834). We further categorized the overall telomere lengths using the 50% value in the controls as cutoff points and found that short overall telomere length was associated with significantly increased EC risks [adjusted odds ration (OR) = 4.72; 95% confidence interval (CI) = 1.85-12.05]. In a tertile analysis, a dose response association was noted between the short overall telomere length and increased EC risk (p for trend = 0.004).The joint effect on EC risk between telomere length and smoking status was also identified. Using never smokers with long telomere length as the reference group, we found that ever smokers with long telomere length, never smokers with short telomere length and ever smokers with short telomere length exhibited significantly increased EC risk with ORs (95% CI) of 3.83 (1.06-13.85), 4.93 (1.21- 20.14), and 10.65 (2.94-38.56), respectively. Our findings provide the first evidence linking short overall and individual telomere lengths of 17p and 12q in PBLs to elevated EC risk, which warrants further investigation in large-size studies.