Genetic 'red flags' for colorectal cancer

BALTIMORE, March 13 (UPI) -- New findings reported Thursday show a simple blood test for genetic red flags could identify people at risk of colorectal cancer, the second-leading cancer killer in the United States.

Researchers said this test might reduce the need for uncomfortable colon and rectal exams.

"While much work still needs to be done before we can prove that this is such a test, it would be exciting to be able to identify people at risk of developing cancer before they get cancer," researcher Andrew Feinberg, a geneticist at Johns Hopkins University in Baltimore, told United Press International.

Colorectal cancer is expected to kill more than 57,000 people in the United States in 2003, making it second only to lung cancer when it comes to U.S. cancer-linked deaths.

While colorectal cancer develops with few or no symptoms at first, colonoscopies and similar medical exams can detect precancerous growths called polyps before they become life threatening.

"I've had a colonoscopy done, and it's no fun, but everyone should do it," Feinberg said. If colorectal cancer is found early, some 90 percent of all patients survive.

Earlier work by Feinberg and colleagues unearthed one of the first genetic defects found to be involved in up to 40 percent of colon cancers. Normally a person inherits two copies of every gene, one from each parent.

So-called "imprinting" compounds usually stick to one of these copies and turn it off, leaving the other copy on. In cancer cases, imprinting patterns can become abnormal, leading to the improper activation of a growth-promoting gene called IGF2, or insulin-like growth factor II.

"When you have LOI (loss of imprinting) of the IGF2 gene in colon cancer, the mother's gene copy gets turned on by mistake and the cell gets a double dose of abnormal cell growth," Feinberg explained.

Feinberg, along with geneticist Hengmi Cui, gastroenterologist Marcia Cruz-Correa and colleagues, investigated blood samples from 172 colonoscopy patients. In findings reported March 14 in the journal Science, they found the odds of finding specific LOI markers were five times greater in patients with family histories of colorectal cancer. Patients with a personal history of colorectal cancer were nearly 22 times more likely to have these markers.

"We were very happy to find this," Feinberg said. "There are no tests that identify risk of cancer right now."

He cautioned this blood test still has some five years to go before scientists can say for sure it predicts colorectal cancer risk. For one thing, long-term studies are needed to confirm whether patients identified as high risk actually do -- or do not -- go on to have increased colorectal cancer rates.

"We need to perfect the test, do more experiments to make this test even more streamlined, easier to do, cheaper. We need to extend these experiments to more patients and different patient populations to validate these results," Feinberg added.

Gastroenterologist C. Richard Boland at Baylor University Medical Center in Dallas found the findings "very interesting" and "worthy of a clinical trial, I should think."

Clinical epidemiologist David Ransohoff at the University of North Carolina in Chapel Hill added: "The development of a non-invasive test for cancer has been the holy grail of cancer detection research for three decades."

In the meantime, Feinberg urged everyone at risk for colorectal cancer to undergo screening. A Centers for Disease Control and Prevention study released Thursday finds that while more than a third of deaths from colorectal cancer could be avoided if people aged 50 and older were examined regularly, only about half of all U.S. men and women in that age group had any type of screening.

The investigators also hope future studies reveal therapies to correct the improper imprinting patterns to fight cancer.

"It's easier to imagine coming up with a drug that affects imprinting than to change a DNA mutation back to normal," Feinberg said.

(Reported by Charles Choi, UPI Science News, in New York.)