Abstract 2554: Constitutive short telomere length and lung cancer risk: a large case- control study.

Abstract

Abstract Background: Telomeres plays a key role in the maintenance of chromosomal stability and integrity. Telomere dysfunction is a common crucial event in malignant transformation and tumorigenesis. Short telomere length in surrogate tissues (peripheral blood leukocytes, or PBLs) has been associated with increased risks of several cancers. In this study, we used a large case control study to evaluate the association of overall telomere length in PBLs with the risk of lung cancer. Methods: We measured the overall telomere lengths in PBLs using real-time quantitative PCR method in a large case-control study with 769 Caucasian lung cancer cases and 769 age, gender, and ethnicity matched healthy controls Wilcoxon rank sum test was used to compare the differences between case patients and control subjects. Unconditional multivariate logistic regression analysis was used to assess the association between telomere length and lung cancer risk. In addition, the effect of age, gender and smoking status was evaluated and correlation analyses between variables were performed. Results: As expected, telomere length was inversely correlated with age in both cases and controls. Lung cancer patients had significantly shorter overall telomere lengths (mean ± standard deviation: 1.20 ±0.37 versus 1.25 ±0.35 p =0.002) than controls, which was only evident in men (1.15 ±0.36 versus 1.24 ±0.36 p <0.001) but not in women. Multivariate logistic regression analysis showed that short overall telomere length was associated with a dose-dependent increase in lung cancer risk. Compared to the individuals within the highest quartile of telomere length, the OR for those within the 3rd, 2nd and 1st quartiles was 0.88 (95% CI 0.65-1.18), 1.08 (95% CI 0.80-1.44) and 1.49 (95% CI 1.12-1.99), respectively (p for trend < 0.001). This effect was more pronounced in current and former smokers (p for trend < 0.001) than in nonsmokers. There was a significant interaction between smoking and overall telomere length in elevating lung cancer risk (p for interaction <0.001). Conclusions: This is the largest epidemiological study to evaluate constitutive telomere length and lung cancer risk. Our data strongly support the role of telomere dysfunction in lung carcinogenesis, highlighting its specific interaction with smoking. Citation Format: Beatriz Sanchez-Espiridion, Jian Gu, David W. Chang, Joe Y. Chang, Charles Lu, Jack A. Roth, Xifeng Wu. Constitutive short telomere length and lung cancer risk: a large case- control study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2554. doi:10.1158/1538-7445.AM2013-2554