A new generation of DNA tests for colon cancer seems likely to improve the detection both of cancers and of the precancerous polyps that precede them. The tests, if validated, could reduce the burden of disease substantially by detecting tumors at an early stage, including those not picked up by a colonoscopy.

Colorectal cancers tend to grow slowly and are easily removed if caught early. But many people over 50 do not comply with the recommendation to have a colonoscopy — a time-consuming procedure in which a tube is threaded up the intestine — and even colonoscopies do not catch everything. Colorectal cancer has become the second most common cancer in the United States; each year it causes more than 50,000 deaths and costs about $14 billion to treat.

Colon tumors provide considerable evidence of their presence by shedding blood and cells that are detectable in the stool. Tests for blood have reduced deaths from colorectal cancer only modestly, because they are not very sensitive to precancerous polyps, the stage at which cancer is best prevented.

Researchers turned to measuring mutations in DNA after Dr. Bert Vogelstein of Johns Hopkins University discovered the series of mutations by which a colon polyp advances to full cancer. But no single mutation predicts a patient’s risk, and the mutation tests, though more accurate than the blood tests, have not been a decisive improvement.

By 2004 it was clear that looking for the Vogelstein mutations was “neat biology but not a home run,” said Dr. David Ransohoff, an expert on colon cancer screening at the University of North Carolina.

A new generation of tests being developed depends on a different process in cancer cells. All cells switch off the genes they do not need by attaching small chemicals called methyl groups to certain sites along their DNA. In cancer cells, there is generally less methylation than usual, except for certain regions of DNA where the methylation process is taken to excess, perhaps because the cells need to shut down tumor suppressor genes. These and other genes are highly methylated in colon tumors and other kinds of cancer.

Exact Sciences, a company based in Madison, Wis., is developing a colon cancer test based on highly methylated DNA. Its researchers reported last month that by testing for methylated DNA at four markers, pieces of DNA drawn from specific genes, they could detect colon tumors and polyps, distinguishing them from normal tissue with 100 percent sensitivity and with no false positives.

The tests of methylated DNA were performed directly on tumors and are expected to be less accurate in the real world, in which they would have to work in stool samples. Almost all of the DNA in stool is from bacteria, and the methylated DNA is a fraction of the 0.01 percent that is human DNA.

Still, Kevin T. Conroy, chief executive of Exact Sciences, said he expected that the four-marker test, when applied to stool samples, would detect at least half of all precancerous polyps and 85 percent of actual cancers. Results of a trial now under way in 1,600 patients will be reported in October, he said.

The test would cost less than $300, and samples could be collected at home. Patients would be advised to take the test every three years. People with a positive result would then have a colonoscopy to verify and remove any polyps, with the result that colonoscopies could be focused on high-risk patients instead of the population at large.

Exact Sciences’ test is based on work by Dr. Vogelstein, Dr. Sanford Markowitz at Case Western Reserve University and Dr. David A. Ahlquist of the Mayo Clinic. Dr. Ahlquist, who is a scientific adviser to the company, identified some of the highly methylated genes the company is testing as markers for colon cancer.

Dr. Ahlquist said that if the test worked as well as hoped on stool samples, “this will be the first noninvasive test that will reliably detect malignant lesions.” Cervical cancer has been virtually eliminated by the Pap test, he said, and “we feel that colon cancer could be eliminated to the same extent.”

The four-marker test can pick up a kind of precancerous tissue called a serrated polyp which is often missed by colonoscopies, Dr. Ahlquist said. It also ignores most innocuous small polyps.

Using different sets of four markers, other kinds of cancer can be detected. “We can detect all of the cancers above the colon — pancreas, esophagus, stomach, bile duct,” Dr. Ahlquist said. Thus in principle, all the cancers of the gastrointestinal tract, which account for nearly a quarter of all cancer deaths in the United States, should be detectable from stool samples.

Dr. Vogelstein said tests for DNA mutations would be better in theory than tests for DNA methylation because “mutations are entirely specific and they are what is driving the tumor”; the methylation is less causative and increases naturally with age.

But the DNA methylation tests are promising in principle, he said, and it seems feasible for Exact Sciences to get a sensitivity of better than 90 percent and a false positive rate of only 5 to 10 percent. “We can tolerate 5 to 10 percent false positives because those people will just get colonoscopies,” he said.

For cancers above the colon, there are many enzymes that digest DNA, so whether such cancers can be detected efficiently can be answered only with experiments, Dr. Vogelstein said. And false positives would be more of a problem, since for these cancers there is no easy verification method like colonoscopy. “That’s when these false positives really start to be the devil,” he said.

Dr. Ransohoff said the Exact Sciences test was still at a preliminary point. “This is neat and it’s promising,” he said. “But we’ve been down this road before and we need to be hopeful without being carried away.”