Anthracotic index and DNA methylation status of sputum contents can be used for identifying the population at risk of lung carcinoma

Cancer. 2004 Dec 25;102(6):348-54. doi: 10.1002/cncr.20643.


Background: Sputum cytology for the mass screening of lung carcinoma is a noninvasive, repeatable, and useful examination, but the detection rate is usually < 0.05% and the reliability is not high.

Methods: The anthracotic index (AI) and methylation status of the promoter regions of the p16, adenomatous polyposis coli (APC), and retinoic acid receptor-beta (RARbeta) genes were examined in 356 sputum specimens after routine cytologic examination.

Results: The mean AI of specimens from males was significantly higher than that from females. AI increased with increasing age and smoking index. The mean AI of patients with lung carcinoma was significantly higher than that of the nonaffected population. Furthermore, the mean AI of the specimens with or without cancer cells from patients with cancer was significantly higher than that of the nonaffected population. Abnormal methylation of the p16, APC, and RARbeta genes was detected in 21.7%, 28.2%, and 26.9% of specimens from patients with cancer, respectively. These ratios were significantly higher than those of the nonaffected populations (0%, 3.9%, and 7.6%, respectively). The incidences of abnormal methylation of the three genes were not associated with histologic classification, smoking index, gender, age, or occupation.

Conclusions: These findings suggested that the AI and abnormal methylation status were useful for identifying a population at risk of lung carcinoma using mass screening of cytology specimens.

MeSH terms

  • Aged
  • Biomarkers / analysis
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Small Cell / etiology
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / pathology*
  • DNA Methylation*
  • Female
  • Genes, APC
  • Genes, p16
  • Humans
  • Lung / pathology*
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Promoter Regions, Genetic
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Risk Factors
  • Sputum / cytology


  • Biomarkers
  • Receptors, Retinoic Acid
  • retinoic acid receptor beta