Telomere Dysfunction: A Potential Cancer Predisposition Factor (original) (raw)

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Correspondence to: Xifeng Wu, MD, PhD, Department of Epidemiology, Box 189, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 (e-mail: xwu@mdanderson.org).

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Received:

13 December 2002

Revision received:

30 May 2003

Published:

20 August 2003

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Xifeng Wu, Christopher I. Amos, Yong Zhu, Hua Zhao, Barton H. Grossman, Jerry W. Shay, Sherry Luo, Waun Ki Hong, Margaret R. Spitz, Telomere Dysfunction: A Potential Cancer Predisposition Factor, JNCI: Journal of the National Cancer Institute, Volume 95, Issue 16, 20 August 2003, Pages 1211–1218, https://doi.org/10.1093/jnci/djg011
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Abstract

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 [CI] = 0.5 to 1.2 kb; P<.001). Nine percent of patients with head and neck cancer were in the longest quartile of telomere length, whereas 59% were in the shortest quartile. Similar patterns were observed for lung, renal cell, and bladder cancer. When subjects were categorized into telomere length quartiles defined by the distribution in control subjects, the following inverse relationship between telomere length and cancer risk was observed: adjusted odds ratios [ORs] for decreasing quartiles = 0.84 (95% CI = 0.36 to 1.97), 1.77 (95% CI = 0.72 to 4.36), and 5.11 (95% CI = 1.90 to 13.77). In stratified analysis, we found a suggestive greater-than-additive interaction between smoking status and telomere length: for ever smokers with short telomeres, OR = 25.05 (95% CI = 6.91 to 90.73); for never smokers with short telomeres, OR = 6.18 (95% CI = 1.72 to 22.13); and for ever smokers with long telomeres, OR = 6.49 (95% CI = 1.54 to 27.38). Telomere length was statistically significantly and inversely associated with baseline and mutagen-induced genetic instability. Conclusion: Short telomeres appear to be associated with increased risks for human bladder, head and neck, lung, and renal cell cancers.

© Oxford University Press

Topic:

• smoking
• lung
• cancer
• head and neck cancer
• renal cell carcinoma
• comet assay
• lymphocytes
• telomere
• urinary bladder
• telomere shortening

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