A long-awaited federal study of an X-ray alternative to the dreaded colonoscopy confirms its effectiveness at spotting most cancers, although it was far from perfect.

Medicare is already considering paying for this cheaper, less intrusive option that could persuade more people to get screened for colon cancer. And some experts believe the new method may boost the 50 percent screening rate for a cancer that is the country’s second biggest killer.

“We’re talking about for the first time really screening the population,” said Dr. Carl Jaffe, an imaging expert at the National Cancer Institute who was not involved in the research.

In the new study, the largest of its kind, the so-called “virtual colonoscopy” identified nine out of 10 people who had cancers and large growths seen by regular colonoscopies.

But there were flaws, too. Among them: The radiologists sometimes misread the X-ray, leading them to spot polyps that weren’t there. That led to unnecessary follow-up testing.

The X-ray test’s real value may be in showing who really needs a regular colonoscopy — it was better at ruling cancer out than it was at detecting it, suggests the report in Thursday’s New England Journal of Medicine.

Colorectal cancer will claim about 50,000 lives this year. The point of screening, widely recommended at age 50, is to find growths before they turn cancerous.

The gold standard is colonoscopy, in which a long, thin tube equipped with a small video camera is snaked through the large intestine to view the lining. Any growth can be removed during the procedure.

It involves sedation and a missed day of work, not to mention preparation that uses pills or liquids to clean out the bowel.

The study focused on CT colonography, also known as virtual colonoscopy. It’s a super X-ray of the colon that is quicker, cheaper and easier on the patient than traditional colonoscopies.

It too requires the bowel clean-out and has a potentially serious drawback — radiation.

Colonoscopies cost up to $3,000. The X-ray test costs $300 to $800; most insurers don’t cover it so far, but Medicare is considering it.

Insurers likely will weigh the new study heavily in their coverage decisions, said Dr. Durado Brooks, who oversees colorectal and prostate cancer programs at the American Cancer Society.

Preliminary, unpublished data from the new study already helped persuade the cancer society and others to put out guidelines in March that added virtual colonoscopy and a stool DNA test to the recommended arsenal of screenings for colon cancer, Brooks said.

In the new study, both the standard colonoscopy and the X-ray test were given to 2,531 people at 15 U.S. medical centers.

The scans showed large growths in about one in six people, although some were false alarms not confirmed by colonoscopy.

Of the patients with growths verified by colonoscopy, 90 percent were flagged through the X-ray scans.

“That’s very good news,” said Dr. C. Daniel Johnson, the lead author of the study. He is a researcher at the Mayo Clinic campus in Scottsdale, Ariz., with financial ties to one virtual colonoscopy company, GE Healthcare.

Back to the false alarms — only one in four of those patients diagnosed with a growth actually had one, noted Dr. Robert Fletcher, a retired Harvard Medical School professor who wrote an editorial accompanying the study. He is a paid consultant for a company that makes a DNA screening test for colon cancer.

Some additional drawbacks to virtual colonoscopy:

_In about one in six of the patients, the X-ray found abnormalities outside the colon that led doctors to recommend additional testing or care. Some of those discoveries may be life-threatening, but others are not and investigation of them may prove expensive and hard on the patient, Fletcher wrote.

_The X-ray tests are not as good at colonoscopy at detecting flat growths on the colon wall that are more likely to be cancerous than the more familiar knobby polyps, according to other researchers.

_Virtual colonoscopies, currently recommended every five years, expose people to repeated doses of radiation. It’s half the dose of a standard CT exam, but the cumulative effects are not yet known. Colonoscopy is only recommended every 10 years.

“These concerns do not rule out CT colonography as a screening test but they need to be considered,” Fletcher wrote.

The study was not designed to look at whether the screenings prevented deaths.

New England Journal: http://nejm.org

Demonstrating that despite the large number of cancer-causing genes already identified, many more remain to be found, scientists at Dana-Farber Cancer Institute have linked a previously unsuspected gene, CDK8, to colon cancer.

The discovery of CDK8’s role in cancer was made possible by new tools for assessing the activity of specific genes, say the authors of the new study. As these tools are further improved, the stream of newly discovered cancer genes is expected to increase, providing new avenues for therapy, the authors suggest. The findings are being published as an advanced online publication by the journal Nature on Sept. 14.

“This study provides confirmation that many of the genes involved in cancer have yet to be identified,” remarked the study’s senior author, William Hahn, MD, PhD, of Dana-Farber and the Broad Institute of Harvard and M.I.T. “When it comes to identifying gene targets for therapy, we’ve really only scratched the surface.”

The study is noteworthy in another respect, as well, the authors indicated. Many of the abnormal proteins linked to cancer are known as “transcription factors” because they’re able to “read″ cell DNA and use that information for producing other cell proteins. Although transcription factors are important regulators, this class of proteins has proven to be impossible to target with drugs. Genes that influence such transcription factors, however, make attractive targets for drugs, since they can potentially disrupt the cancer process and disable tumor cells. CDK8 is such a gene.

The new study began with a focus on a protein called beta-catenin, a transcription factor that is overactive in nearly all colorectal cancers. Although overactive beta-catenin plays a role in the initial formation of tumors, other genetic abnormalities must occur for tumors to become fully malignant.

To determine which genes control the production of beta-catenin and are involved in the proliferation of colon cancer cells, the research team ran three screening tests. In the first two, they used RNA interference to shut down more than a thousand genes one by one and recorded the instances where beta-catenin activity decreased and the cells stopped growing. They then analyzed colon cancers for genes that had extra copies. When they examined where the results of the three tests overlapped, one gene stood out — CDK8, explained Hahn, who is also an associate professor of medicine at Harvard Medical School

The protein produced from CDK8 is part of the “mediator complex,” a conglomeration of proteins that serves as a bridge for compounds involved in gene transcription. “This study demonstrates that blocking CDK8 interferes with the proliferation of colon cancer cells that have high levels of the CDK8 protein and overactive beta-catenin,” Hahn said. “Drugs that target CDK8 may be very useful against tumors whose growth is driven by beta-catenin.”

Hikes risk of developing cancer to 50 percent

About one-third of colorectal cancers are inherited, but the genetic cause of most of these cancers is unknown. The genes linked to colorectal cancer account for less than 5 percent of all cases.

Scientists at Northwestern University’s Feinberg School of Medicine and colleagues have discovered a genetic trait that is present in 10 to 20 percent of patients with colorectal cancer. The findings strongly suggest that the trait is a major contributor to colorectal cancer risk and likely the most common cause of colorectal cancer to date.

If a person inherits this trait — which is dominant and clusters in families — the study found the lifetime risk of developing colorectal cancer is 50 percent, compared to 6 percent for the general population. The study will be published August 14 in an advanced on-line report in the journal Science.

“This probably accounts for more colorectal cancers than all other gene mutations discovered thus far,” said Boris Pasche, M.D., a lead author of the paper and director of the Cancer Genetics Program at the Feinberg School and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Pasche also is a physician at Northwestern Memorial Hospital.

“The reasonable expectation is this finding will save some lives,” Pasche said. “We will be able to identify a larger number of individuals that are at risk of colorectal cancer and, in the long term, maybe decrease the cases of colorectal cancer and of people dying from it by being able to screen them more frequently.”

Colorectal cancer is the second leading cause of cancer death in the U.S.

The trait, which has been named TGFBR1 ASE, results in decreased production of a key receptor for TGF-beta, the most potent inhibitor of cell growth. With less of this vital protective substance to inhibit cell growth, colon cancer can more easily develop.

In 1998, Pasche and colleagues discovered the first mutation of this gene and in 1999 they showed that it was linked to a higher risk of colorectal cancer.

The results presented in this new study are the first to show that decreased production of this receptor for TGF-beta was present in 10 to 20 percent of patients with colorectal cancer. Decreased production of the same receptor was present in only 1 to 3 percent in healthy control groups.

The findings, which are based on a Caucasian population, need to be confirmed in other studies and may show strong variation between ethnic groups, Pasche said.

Pasche expects that a clinical test will soon be developed that could be offered to families with a history of colorectal cancer and other individuals to determine whether they carry this mutation.

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