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Background: Genetic instability associated with telomere dysfunction (i.e., short telomeres) is an early event in tumorigenesis. We investigated the association between telomere length and cancer risk in four ongoing case–control studies. Methods: All studies had equal numbers of case patients and matched control subjects (92 for head and neck cancer, 135 for bladder cancer, 54 for lung cancer, and 32 for renal cell carcinoma). Telomere length was measured in peripheral blood lymphocytes from study participants. Genetic instability was assessed with the comet assay. Patient and disease characteristics were collected and analyzed for associations with risk for these cancers. All statistical tests were two-sided. Results: Telomeres were statistically significantly shorter in patients with head and neck cancer (6.5 kilobases [kb]) than in control subjects (7.4 kb) (difference = 0.9 kb, 95% confidence interval …