A prospective study of telomere length measured by monochrome multiplex quantitative PCR and risk of lung cancer.

PURPOSE Telomere length plays an important role in chromosomal stability and tumorigenesis, and its measurement in peripheral white blood cell DNA may be a predictor of the development of lung cancer. EXPERIMENTAL DESIGN Using a new method - monochrome multiplex quantitative PCR - which reduces measurement variability, we compared telomere length relative to standard DNA in white blood cell DNA in 229 incident male lung cancer cases and 229 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers. RESULTS Median (10th, 90th percentile) telomere length was 1.13 (0.86, 1.45) in cases and 1.08 (0.85, 1.38) in controls (P=0.038). Telomere length was inversely associated with pack-years of smoking (Spearman's correlation r=-0.16, P=0.02) among controls. Compared to subjects with shorter telomere length (≤median), subjects with greater telomere length (>median) had a 1.6-fold (95% CI, 1.06-2.36) increased risk of lung cancer. There was a significant linear relationship between quartiles of telomere length and risk of lung cancer (odds ratios (95% confidence intervals) by quartile: 1.00, 0.98 (0.55-1.73), 1.62 (0.95-2.77), and 1.50 (0.84-2.68); P(trend)=0.05). In addition, subgroup analysis showed that greater telomere length was associated with an increased risk of lung cancer among longer-term smokers (>38 years) (OR, 1.90; 95% CI, 1.00-3.59) but not among shorter-term smokers (≤38 years) (OR, 1.08; 95% CI, 0.56-2.11) (P(interaction)=0.01). CONCLUSIONS Our results suggest that greater telomere length may be associated with higher risk of lung cancer among male smokers.