Chromosomal instability is one of the early hallmarks of human carcinogenesis. Shortened telomeres may predispose to chromosomal instability leading to the development of some cancers, including esophageal adenocarcinoma (EAC). However, whether the telomere changes associated with cancer risk occur at the global or chromosome-specific level remain largely unknown. Here, we developed a novel two-step quantitative fluorescent in situ hybridization (FISH) assay to measure the overall and genome-wide chromosome-specific telomere length in peripheral blood lymphocytes (PBLs). In this assay, overall telomere FISH is first carried out using peptide-coupled nucleic acid (PNA) probe. The relative intensity of each telomere signal is obtained by digital capture of the microscopic image and quantified. Then we perform the second FISH with centromere and subtelomere probes on the same slide to label each chromosome. Therefore, we can identify and quantify the telomere length for the p arm or q arm of each chromosome. We next used this assay to measure the overall and chromosome specific telomere length in a pilot case-control study of 31 EAC cases and 31 matched controls. We found EAC patients had significantly shorter overall telomere lengths in PBLs compared with controls (P = 0.039). Notably, the chromosome-specific telomeres of 8, 10, 14, 16, 17, and 22 were significantly shorter in cases than in controls (P < 0.05). Analysis of chromosome arm-specific telomeres indicated that the telomere lengths of 17p, 17q, 16q, Xp, and 10q, and 13p were shorter in cases than controls (P < 0.04). Cumulative analysis of these six significant telomeres showed that the total length for cases was significantly shorter than controls (P < 0.001). Using median expression as cutoff, we found that patients with short telomeres on chromosome 17, 13p, 22q, or Xp had 4.4-fold increased risk of EAC (P for trend < 0.001). Taken together, our study provides the first epidemiologic evidence that cancer cases have generally short telomeres across all chromosome arms and suggests that short telomeres in specific chromosome arms may exhibit stronger cancer predisposing effects than others depending on cancer types.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):B42.