Short leukocyte telomere length, alone and in combination with smoking, contributes to increased risk of gastric cancer or esophageal squamous cell carcinoma.

In humans, telomeres shorten along with division of somatic cells. Shortened telomere length might result in genomic instability and has been associated with several malignancies. However, the findings in different populations remain conflicting. Therefore, we assessed the association of telomere length in peripheral blood leukocytes with risk of gastric cancer (GC) or esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. A total of 574 GC cases, 740 ESCC cases and 774 age- and sex-matched healthy controls were included in this analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. The GC or ESCC patients had significantly shorter relative telomere length (RTL) (median ± SD: GC: 1.20 ± 0.42; ESCC: 1.27 ± 0.48) than controls (1.41 ± 0.58). Four-fold increased GC risk (OR = 4.10, 95% CI = 2.78-6.05, P = 1.10 × 10-12) or 1.56-fold increased ESCC risk (95% CI = 1.12-2.18, P = 0.009) among subjects in the shortest quartile of telomere length was found compared with the highest quartile. We also observed a cumulative effect between short RTL and smoking in intensifying risk of GC (P = 4.50 × 10-9) or ESCC (P = 5.92 × 10-33). Moreover, there were cumulative effects between RTL, smoking and drinking in elevating risk of GC (Ptrend = 0.001) or ESCC (Ptrend = 1.57 × 10-32). Interestingly, RTL-related rs621559 and rs398652 genetic variants are significantly associated with GC risk. These results indicate that short RTL is involved in susceptibility to developing GC or ESCC, alone and in a gene-environment interaction manner. Short telomere length might be a potential molecular marker, in combination with lifestyle risk factors, to identify high-risk individuals.