Abstract 4160: Telomere length in white blood cell DNA and lung cancer: a pooled analysis of three prospective cohorts

Background: There is growing evidence that longer telomere length is associated with higher risk of lung cancer. We investigated this association in the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which was conducted in the United States. We also combined these data with two previously published prospective cohorts: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) trial conducted among ever smoking males in Finland and the Shanghai Women's Health Study (SWHS) which comprised primarily of never-smoking women, resulting in a pooled analysis on a total of 847 cases and 847 controls matched by age, sex and study. Methods: Blood samples were collected prior to diagnosis of lung cancer and telomere length was measured using the same monochrome multiplex quantitative PCR method in all three studies. We used conditional logistic regression models to calculate odds ratios (OR) and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk adjusted for age, to account for residual confounding, and pack-years of smoking as continuous variables. Analyses by telomere length quartile retaining the initial categorization used in each study, and using categorization based on telomere length in pooled controls, produced similar findings and results are presented for the former. Results: In the PLCO Trial, increasing telomere length was significantly associated with lung cancer risk (adjusted OR [95% CI] by quartile: 1.00; 1.11 [0.65-1.92]; 1.20 [0.66-2.15]; and 1.83 [1.05-3.19]; P-trend = 0.011), consistent with results from the ATBC and SWHS studies. In the pooled analyses, the adjusted OR (95% CI) by quartile was 1.00; 1.24 (0.90-1.72); 1.27 (0.91-1.77); and 1.87 (1.33-2.63); P-trend = 0.000022. This positive association was particularly evident for adenocarcinoma cases, especially those diagnosed more than 6 years after blood collection (n=115; adjusted OR [95% CI] by quartile: 1.00; 2.48 [0.85-7.23]; 2.05 [0.81-5.15]; and 3.59 [1.38-9.34]; P-trend = 0.0027). Conclusion: Telomere length in white blood cell DNA may be an important biomarker of future increased risk of lung cancer in diverse populations. Citation Format: Wei Jie Seow, Richard Cawthon, Mark Purdue, Wei Hu, Yu-Tang Gao, Wen-Yi Huang, Stephanie J. Weinstein, Bu-Tian Ji, Jarmo Virtamo, Dean Hosgood, Bryan Bassig, Xiaoou Shu, Qiuyin Cai, Yongbin Xiang, Shen Min, Wong-Ho Chow, Sonja Berndt, Christopher Kim, Unhee Lim, De