Smoking and drinking can induce p15 methylation in the upper aerodigestive tract of healthy individuals and patients with head and neck squamous cell carcinoma

Cancer. 2004 Jul 1;101(1):125-32. doi: 10.1002/cncr.20323.


Background: The consumption of tobacco and alcohol has been implicated in the development of head and neck squamous cell carcinoma (HNSCC). Promoter methylation of tumor suppressor genes is common in HNSCC. In this study, the authors evaluated the effects of tobacco and alcohol on p15 gene methylation of cells in cells from the mouth and throat of physically healthy individuals and patients with HNSCC.

Methods: The study participants were divided into 3 groups, including a group of 37 healthy nonsmokers and nondrinkers, a group of 22 healthy smokers and/or drinkers and a group of 31 patients with HNSCC.

Results: Methylation of p15 was detected in cells obtained from mouth and throat (M&T) rinsing fluid samples from 3 of 37 healthy individuals (8%) who did not drink or smoke, from 15 of 22 healthy smokers and/or drinkers (68%), and from 15 of 31 patients (48%) with HNSCC. Among 31 patients with HNSCC, 20 patients (65%) had methylated p15 gene in their tumor biopsies. With the use of beta-actin as a reference, the ratio of methylated p15 to beta-actin was calculated as an index of the percentage of cells with p15 methylation. The percentage of exfoliated cells from M&T rinsing fluid samples that had p15 methylation ranged from 0% to 11% for patients with HNSCC and from 0% to 21% for healthy smokers/drinkers, respectively. The methylation index of tumor cells with p15 methylation ranged from 0% to 65%.

Conclusions: The results suggest that p15 gene methylation can be induced by chronic smoking and drinking and may play a role in the very early stages of carcinogenesis in HNSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / adverse effects*
  • Base Sequence
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • DNA Methylation*
  • Female
  • Genes, Tumor Suppressor / drug effects*
  • Head and Neck Neoplasms / etiology*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mouth / drug effects
  • Mouth / pathology
  • Pharynx / drug effects
  • Pharynx / pathology
  • Promoter Regions, Genetic / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking / adverse effects*