Quantitative assessment of lung cancer associated with genes methylation in the peripheral blood

Lung cancer is the leading cause of cancer-related deaths worldwide due mainly to late diagnosis and poor prognosis. Aberrant promoter methylation is an important mechanism for silencing of tumor suppressor genes during carcinogenesis and a promising tool for the development of molecular biomarkers.

We evaluated the p16, RASSF1A, and FHIT genes promoter methylation status in peripheral blood DNA between 200 lung cancer patients and 200 normal controls by using SYBR green-based quantitative methylation-specific PCR (qMSP).

There were statistically significant differences in the methylation status of p16, RASSF1A, and FHIT between the cancer cases and controls (p16: P = .008, RASSF1A: P = .038, FHIT: P = .002). When the subjects were categorized into quartiles based on the genes methylation status, the risk of lung cancer was found to increase as methylation status increased (p16: Ptrend = .002, RASSF1A: Ptrend = .014, FHIT: Ptrend = .001). When the median of methylation status was used as the cutoff between high and low methylation status, individuals with high methylation status were at a significantly higher risk of lung cancer than those with low methylation status (p16: adjusted odds ratio = 1.597, P = .028; RASSF1A: adjusted odds ratio = 1.551, P = .039; FHIT: adjusted odds ratio = 1.763, P = .008). In addition, there were no significant correlations between p16, RASSF1A, or FHIT methylation status and gender (P > .05), age (P > .05), smoking history (P > .05), histological type (P > .05), or clinical stage (P > .05).

These results suggest that the high methylation statuses of p16, RASSF1A, or FHIT genes were associated with a significantly increased risk of lung cancer; the risk of lung cancer increased as the methylation status increased. Further investigation of their definitive usefulness in clinical practice is warranted.