Lung cancer risk stratification using methylation profile in the oral epithelium.

Background: Assuming that the entire airway is affected by the same inhaled carcinogen, similar molecular alterations may occur in the lung and oral cavity. Thus, we hypothesized that DNA methylation profiles in the oral epithelium may be a promising biomarker for lung cancer risk stratification.

Methods: A methylation-specific polymerase chain reaction was performed on oral epithelium from 16 patients with lung cancer and 32 controls without lung cancer. Genes showing aberrant methylation profiles in the oral epithelium were compared between patients and controls.

Results: The analysis revealed that HOXD11 and PCDHGB6 were methylated more frequently in patients than in controls ( p = 0.0055 and p = 0.0247, respectively). Combined analyses indicated that 8 of 16 (50%) patients and 3 of 32 (9.4%) controls showed DNA methylation in both genes ( p = 0.0016). Among the population limited to current and former smokers, 6 of 11 (54.5%) patients showed methylation in both genes, compared to 1 of 17 (5.9%) controls ( p = 0.0037). In a subgroup analysis limited to the population above 50-years old, 8 of 16 (50%) patients and 2 of 16 (12.5%) controls showed methylation in both genes ( p = 0.0221).

Conclusions: The results of this study indicate that specific gene methylation in the oral epithelium might be a promising biomarker for lung cancer risk assessment, especially among smokers. Risk stratification through the analysis of DNA methylation profiles in the oral epithelium may be a useful and less invasive first-step approach in an efficient two-step lung cancer screening strategy.