• Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland; weijie.seow2@nih.gov.
• Department of Human Genetics, University of Utah, Salt Lake City, Utah;
• Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
• Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine;
• Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
• Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York;
• Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
• Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; and.
• Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas;
• Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii;

We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex qPCR assay. We used conditional logistic regression models to calculate ORs and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24 (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022]. Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length [OR (95% CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11-4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than 6 years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations.