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Gallstone Medicine Cuts Colon Cancer Risk, UA Study Says

Posted on: Tuesday, 14 June 2005, 09:00 CDT

A drug commonly used to treat gallstones has emerged as a key player in the prevention of colon cancer, a major University of Arizona study has concluded.

After nearly a decade of testing, the drug - known as ursodeoxycholic acid, or UDCA - has proved to reduce the risk of dangerous precancerous growths in the bowel by nearly 40 percent.

Such growths are most likely to develop into full-fledged colon cancer - a leading cause of cancer death in the United States, expected to kill more than 56,000 people this year.

"What we have is a drug that is commercially available, being used regularly, that is now an option for patients who are at very high risk for colon cancer," said Dr. David S. Alberts, director of the Arizona Cancer Center.

It was Alberts who launched the studies of UDCA in the 1990s as part of a $17 million mega-grant from the National Cancer Institute to find and test agents capable of preventing this deadly cancer.

"It is exciting after all these years not only to find out it is effective, but also one of the safest drugs for the digestive tract," Alberts said. "It is extremely well-tolerated, with very few side effects."

The study is being reported in today's Journal of the National Cancer Institute.

As a result of these findings, UDCA - known commercially as Actigall, or ursodiol - may join aspirin and calcium in the growing arsenal of nontoxic agents with proven ability to reduce the risk of colon cancer.

"I don't think this is on the radar screen of most doctors yet, but there's a good chance it will be once the results are out," said Dr. James B. Klein, a Tucson gastrointestinal surgeon who referred high-risk patients to the study. "We will wait for guidance from those who did the study. And it looks like we will want to do more studies to confirm these results.

"But I have to say we support this research," Klein said. "Preventing this cancer is far better than having to treat it."

Another promising candidate, the trace mineral selenium, still is under investigation in UA-led colon cancer prevention studies.

A naturally occurring bile salt, UDCA long has been known to suppress a bile acid linked to the start of the cancer process in the intestine. It has been used for years not only to dissolve gallstones but to treat patients with ulcerative colitis - who are at high risk for colon cancer.

After a series of small, promising studies showed it could reduce the cancer-promoting bile acid in feces, UDCA finally was ready for prime time - a controlled, double-blind, Cancer Institute-funded study of more than 1,200 patients at high risk for colon cancer.

Each of those patients, from the Tucson and Phoenix areas, already had had a precancerous polyp recently removed. For three years, half were given active UDCA pills and the other half inactive placebo pills. Neither the patients nor the researchers knew who got what until the trial ended.

After three years, the recurrence of polyps in all patients taking UDCA was reduced by only 12 percent - about the same as placebo patients, and considered insignificant.

However, for those who had high-grade colon polyps - "one small step away from cancer," in Alberts' words - the risk of recurrence was reduced by 39 percent, a "significant" result, according to the study.

"I think, given the choice, we'd rather see this work against the most dangerous polyps," Alberts said. "At the very least, UDCA is a strong candidate for further study, especially in those at highest risk for developing colorectal cancer."

One who apparently benefited from taking UDCA, Henry Wienold, now 83, has had no new colon polyps since he had one removed just before joining the UA trial.

"I'm glad to hear this turned out well - I didn't know if they would get any results," said Wienold, whose father died of colon cancer. "I had no side effects at all. I just took the pills every day, and nothing bad happened. It was easy to do."

At this point, aspirin has produced the strongest evidence for preventing colon cancer, said Dr. John Cunningham, a UA gastroenterologist.

Most doctors will look for a confirming study "before jumping on the ursodiol bandwagon," he said.

Factors that boost danger

Potential risk factors for colo- rectal cancer:

* A family history of colorectal cancer

* Eastern European Jewish descent (Ashkenazi Jews)

* A personal history of colo- rectal polyps

* A personal history of chronic inflammatory bowel disease

* Age over 50

* A diet mostly from animal sources

* Physical inactivity

* Obesity

* Diabetes

* Smoking

* Heavy use of alcohol

Source: American Cancer Society

To learn more

* To read the full report of the Arizona Cancer Center study in today's Journal of the National Cancer Institute, go to jncicancerspectrum. oupjournals.org/

* Contact reporter Carla McClain at 806-7754 or at cmcclain@azstarnet.com.

Source: Arizona Daily Star

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