Short telomere lengths in peripheral blood leukocytes are associated with an increased risk of oral premalignant lesion and oral squamous cell carcinoma

Cancer. 2013 Dec 15;119(24):4277-83. doi: 10.1002/cncr.28367. Epub 2013 Sep 16.

Abstract

Background: Oral premalignant lesions (OPLs) are precursors of oral squamous cell carcinoma (OSCC). Short telomeres in peripheral blood leukocytes (PBLs) are associated with increased risks of several cancers. However, it is unclear whether short leukocyte telomere length (LTL) predisposes individuals to OPL and OSCC.

Methods: LTL was measured in PBLs from 266 patients who had a diagnosis of either OPL (N = 174) or OSCC (N = 92) and from 394 age-matched and sex-matched controls. The association between LTL and the risk of OPL or OSCC, as well as the interaction of telomere length, cigarette smoking, and alcohol drinking on the risk of OPL or OSCC, were analyzed.

Results: The age-adjusted relative LTL was shortest in the OSCC group (1.64 ± 0.29), intermediate in the OPL group (1.75 ± 0.43), and longest in the control group (1.82 ± 0.36; Ptrend < .001). When the analysis was dichotomized at the median value in controls, adjusting for age, sex, smoking status, and alcohol drinking status, the odds ratio for the risk of OPL and OSCC associated with short LTL was 2.03 (95% confidence interval, 1.29-3.21) and 3.47 (95% CI, 1.84-6.53), respectively, with significant dose-response effects for both associations. Among 174 patients with OPL, 23 progressed to OSCC, and the mean LTL was shorter in progressors than in nonprogressors (mean ± standard deviation: 1.66 ± 0.35 vs 1.77 ± 0.44, respectively), although the difference did not reach statistical significance (P = .258), probably because of the small number of progressors. An interaction analysis identified short LTL, smoking, and drinking alcohol as independent risk factors for OPL and OSCC.

Conclusions: Short LTL was associated with increased risks of developing OPL and OSCC. The current results also indicated that short LTL likely predisposes patients to the malignant progression of OPL.

Keywords: alcohol drinking; oral premalignant lesion; oral squamous cell carcinoma; peripheral blood leukocytes; smoking; telomere length.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / adverse effects
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Humans
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Leukocytes / ultrastructure*
  • Male
  • Middle Aged
  • Mouth Diseases / genetics
  • Mouth Diseases / pathology
  • Mouth Neoplasms / blood
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Precancerous Conditions / blood
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Risk
  • Risk Factors
  • Smoking / adverse effects
  • Squamous Cell Carcinoma of Head and Neck
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere Shortening