Telomere length shortening and gastric cancer risk in a high risk Polish population

Abnormally short telomeres have been associated with chronic inflammation and chromosomal instability. Increased rates of telomere shortening are present in gastric tumor tissue and in gastric epithelium tissue infected with Helicobacter pylori (H. pylori), a known risk factor for gastric cancer. However, no study has examined the role of telomere length in peripheral blood genomic DNA in relation to H. pylori infection and gastric cancer risk. In a population-based study of 300 cases and 416 controls conducted in Warsaw, Poland, between 1994 and 1996, we examined: i) the association between telomere length in peripheral blood genomic DNA and potential gastric cancer risk factors, including H. pylori infection among healthy controls; ii) the risk of gastric cancer associated with shortened telomeres. Telomere length (TL) was measured in duplicate using real-time quantitative PCR. The mean of the two measurements was used to calculate the relative ratio of telomere repeat to single-copy gene number (T/S ratio). We used regression models to obtain age-adjusted p-values for the correlations of telomere length with H. pylori infection and other exposures. Age-adjusted logistic regression models were used to estimate gastric cancer risk associated with telomere length. Among controls, telomere length was significantly shorter in H. pylori-infected individuals (TL=1.32, SD=0.34) than in uninfected subjects (TL=1.44, SD=0.35; p =0.03). We also observed significant inverse correlations of telomere length with age (p<0.001), pack years of cigarette smoking (p=0.003), total years of alcohol consumption (p=0.007), and low weekly fruit intake (p=0.02). When cases and controls were compared, telomere length was significantly shorter in cases (TL=1.25; SD=0.34) than in controls (TL=1.34; SD=0.35) [p=0.0008]. Furthermore, gastric cancer risk was significantly increased with decreasing telomere length (OR=2.00, 95% CI=1.32-3.02 for subjects in the lowest quartile (shortest) of telomere length compared to those in the highest quartile of telomere length; P trend<0.001). Our results suggest that H. pylori infection and other potential gastric cancer risk factors are associated with shorter telomeres. Shortened telomere length was associated with an increased risk of gastric cancer in this high-risk Polish population.