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Leukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus

Departments of ¹ Pathology, ² Medicine, ³ Genome Sciences, and ⁴ Epidemiology, University of Washington; Divisions of ⁵ Human Biology and ⁶ Public Health Sciences, Fred Hutchinson Cancer Research Center; ⁷ Gastroenterology, Virginia Mason Medical Center, Seattle, Washington; and ⁸ Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts

Requests for reprints: Peter S. Rabinovitch, Department of Pathology, University of Washington, Box 357705, 1959 Northeast Pacific Street, K-081 HSB, Seattle, WA 98195-7705. Phone: 206-685-3761; Fax: 206-616-8271. E-mail: petersr{at}u.washington.edu

Purpose: Leukocyte telomere length has gained attention as a marker of oxidative damage and age-related diseases, including cancer. We hypothesize that leukocyte telomere length might be able to predict future risk of cancer and examined this in a cohort of patients with Barrett's esophagus, who are at increased risk of esophageal adenocarcinoma and thus were enrolled in a long-term cancer surveillance program.

Patients and Methods: In this prospective study, telomere length was measured by quantitative PCR in baseline blood samples in a cohort of 300 patients with Barrett's esophagus followed for a mean of 5.8 years. Leukocyte telomere length hazard ratios (HR) for risk of esophageal adenocarcinoma were calculated using multivariate Cox models.

Results: Shorter telomeres were associated with increased esophageal adenocarcinoma risk (age-adjusted HR between top and bottom quartiles of telomere length, 3.45; 95% confidence interval, 1.35-8.78; P = 0.009). This association was still significant when individually or simultaneously adjusted for age, gender, nonsteroidal anti-inflammatory drug (NSAID) use, cigarette smoking, and waist-to-hip ratio (HR, 4.18; 95% confidence interval, 1.60-10.94; P = 0.004). The relationship between telomere length and cancer risk was particularly strong among NSAID nonusers, ever smokers, and patients with low waist-to-hip ratio.

Conclusion: Leukocyte telomere length predicts risk of esophageal adenocarcinoma in patients with Barrett's esophagus independently of smoking, obesity, and NSAID use. These results show the ability of leukocyte telomere length to predict the risk of future cancer and suggest that it might also have predictive value in other cancers arising in a setting of chronic inflammation. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2649–55)