Predicting lung cancer by detecting aberrant promoter methylation in sputum

Despite the promise of using DNA markers for the early detection of cancer, none has proven universally applicable to the most common and lethal forms of human malignancy. Lung carcinoma, the leading cause of tumor-related de ath, is a key example of a cancer for which mortality could be greatly redu ced through the development of sensitive molecular markers detectable at th e earliest stages of disease. By increasing the sensitivity of a PCR approa ch to detect methylated DNA sequences, we now demonstrate that aberrant met hylation of the p16 and/or O-6-methylguanine-DNA methyltransferase promoter s can be detected in DNA from sputum in 100% of patients with squamous cell lung carcinoma up to 3 years before clinical diagnosis. Moreover, the prev alence of these markers in sputum from cancer-free, high-risk subjects appr oximates lifetime risk for lung cancer. The use of aberrant gene methylatio n as a molecular marker system seems to offer a potentially powerful approa ch to population-based screening for the detection of lung cancer, and poss ibly the other common forms of human cancer.