Chromosomal instability, DNA index, dysplasia, and subsite in oral premalignancy as intermediate endpoints of risk of cancer

Cancer Epidemiol Biomarkers Prev. 2013 Jun;22(6):1133-41. doi: 10.1158/1055-9965.EPI-13-0147. Epub 2013 Apr 29.

Abstract

Background: Chromosomal instability and aneuploidy may represent biomarkers of oral exposure to damaging agents and early signs of clinical disease according to the theory of "oral field cancerization."

Methods: The hypothesis was tested that the DNA index (DI) values, obtained by high-resolution DNA flow cytometry (DNA-FCM), may potentially contribute to oral cancer risk prediction. For this purpose, the DI of oral fields of normal-appearing mucosa and oral potentially malignant disorders (OPMDs) in 165 consecutive patients was tested for association with dysplasia and/or the oral subsites of tongue and floor of the mouth taken as high-risk intermediate endpoints surrogate of cancer clinical endpoints. The association was evaluated by logistic regression using patient gender, age, tobacco, cigarette smoking habit, and alcohol abuse as confounding variables.

Results: Different DI models provided evidence of statistical significant associations. Subdividing the DI values in diploid, near-diploid aneuploid, and high or multiple aneuploid from both OPMDs and oral normal-appearing mucosa, ORs, respectively, of 1, 4.3 (P = 0.001), and 18.4 (P < 0.0005) were obtained.

Conclusion: Routine DI analysis by high-resolution DNA-FCM seems potentially useful to complement dysplasia and subsite analysis for assessment of oral cancer risk prediction and for a better management of the patients with OPMDs. Work is in progress to validate the present findings in a prospective study with clinical endpoints.

Impact: Identifying DNA abnormalities in oral premalignancy may lead to biomarkers of oral exposure and cancer risk and potentially to more effective prevention measures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aneuploidy
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / pathology
  • Chromosomal Instability*
  • DNA, Neoplasm / genetics*
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Hyperplasia / etiology
  • Hyperplasia / pathology
  • Leukoplakia, Oral / etiology
  • Leukoplakia, Oral / pathology
  • Male
  • Middle Aged
  • Mouth Mucosa / pathology*
  • Mouth Neoplasms / classification
  • Mouth Neoplasms / etiology*
  • Mouth Neoplasms / pathology
  • Precancerous Conditions / etiology*
  • Precancerous Conditions / pathology
  • Prognosis
  • Risk Factors

Substances

  • DNA, Neoplasm