A molecular marker-based method for monitoring and detecting cancer in humans. Aberrant methylation of gene promoters is a marker for cancer risk in humans. A two-stage, or "nested" polymerase chain reaction method is disclosed for detecting methylated DNA sequences at sufficiently high levels of sensitivity to permit cancer screening in biological fluid samples, such as sputum, obtained non-invasively. The method is for detecting the aberrant methylation of the p16 gene, O 6-methylguanine-DNA methyltransferase gene, Death-associated protein kinase gene, RAS-associated family 1 gene, or other gene promoters. The method offers a potentially powerful approach to population-based screening for the detection of lung and other cancers.
The Government has certain rights to this invention pursuant to National Institutes of Health Grants 50 CA8184 and RO1 CA70190, and pursuant to Cooperative Agreement DE-FC04-96AL76406 and Contract DE-FG02-90ER60939 with the Office of Biological and Environment Research, U.S. Department of Energy.