Hormone therapy offers potential protective effect against colon cancer in older women

DENVER -- In a large study, a national team of researchers led by Mayo Clinic scientists observed that self-reported use of hormone therapy was associated with a significantly lower colorectal cancer risk. However, the mechanisms for the apparent protective association are still unclear.

The study, being presented at the AACR 100th Annual Meeting 2009, was designed to look at possible links between estrogen exposure and colon cancer molecular subtypes, to determine how these hormones might function as anti-cancer agents.

"In our large, prospective study, use of hormone therapy seemed to be beneficial with respect to reducing colorectal cancer risk -- women who did use these drugs had a 28 percent lower incidence rate than women who did not use these drugs," says the study's lead author, David Limsui, M.D., a fellow in the Department of Gastroenterology at Mayo Clinic's campus in Rochester, Minn. "But we still don't know how estrogen compounds work in cancer prevention, which is intriguing."

Women who reported using other hormone preparations, such as oral contraceptives, did not appear to derive any colorectal cancer prevention benefits. "Based on our findings, we need to continue exploring the cancer pathways that might be affected by these hormones," Dr. Limsui says.

He adds that other studies have also found that hormone therapy protects postmenopausal women against colon cancer. The largest randomized clinical trial was the 16,000-participant Women's Health Initiative, which concluded in 2004 that combination hormone therapy (estrogen and progestin) reduced a woman's risk of colorectal cancer by about 40 percent, he says. "But few studies have delved deeper to see how these hormones work at the molecular level," Dr. Limsui says.

This investigation is part of the Iowa Women's Health Study, which enrolled 41,836 women from Iowa, aged 55-69, in 1986. After exclusions, the study group consisted of 37,285 women. In the current study, the investigators examined tumor tissue from 553 colorectal cancer patients, specifically looking for associations between self-reported hormone use and a specific DNA methylation pattern, called the CpG island methylator phenotype, or BRAF gene mutations. No associations were detected between hormone use and these molecular markers. Of note, the investigative team previously reported that certain environmental exposures, such as cigarette smoking, might increase colorectal cancer risk through DNA methylation pathways.

April 22, 2009