Tuesday, May 12, 2009

Aspirin can reduce colorectal cancer risk

Three recent studies confirm that aspirin can reduce colorectal cancer risk:

Aspirin can reduce colorectal cancer risk

A study of Medicare patients with osteoarthritis provides additional evidence that non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin reduce the risk of colorectal cancer. Earlier investigations of the drugs’ impact on tumor development could not rule out the possibility that an observed protective effect was caused by other preventive health care measures. The current study, led by a Massachusetts General Hospital (MGH) physician, appears in the August 2007 Journal of General Internal Medicine.

“This is good news for people who take NSAIDs regularly for osteoarthritis,” says Elizabeth Lamont, MD, MS, of the MGH Cancer Center, the study’s lead author. “Although patients face risks such as bleeding or kidney damage from this therapy, they probably are at a lower risk of developing colorectal cancer.” Because of the risks posed by the dosage used to treat osteoarthritis, she and her co-authors stress that currently available NSAIDs should not be used solely to prevent cancer.

Earlier randomized trials clearly showed that NSAID treatment can prevent the development of precancerous colorectal polyps, but whether or not such therapy also reduces the risk of invasive colorectal cancer has not yet been confirmed. Those trials used relatively low doses of aspirin and showed no significant differences in colorectal cancer rates between the aspirin and placebo groups. While many observational studies have shown a protective effect of NSAIDs against colorectal cancer, interpretation of some of those results may have been clouded by other healthy behaviors of the participants.

Benefits of aspirin to prevent colon cancer

A colon cancer researcher at the Ireland Cancer Center of University Hospitals Case Medical Center (UHCMC) has laid out the roadmap for how medical science should employ aspirin and new aspirin-like drugs for use in preventing colon cancer in certain high-risk individuals.

In today's New England Journal of Medicine, Sanford Markowitz, MD, PhD, writes an editorial accompanying research from Dr. Charles Fuchs' team at Harvard Medical School that lays out the hypothesized mechanism by which the use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), also called COX-2 inhibitors, act to decrease the risk of developing colon cancer.

"The compelling evidence that chronic use of aspirin or certain NSAIDS can substantially lower the risk of colon cancer has important implications, especially because colon cancer is the second leading cause of cancer death," writes Dr. Markowitz, the Francis Wragg Ingalls Professor of Cancer Genetics at UHCMC and Case Western Reserve University School of Medicine.

In the Journal article, the Harvard researchers' findings demonstrated that two-thirds of colon cancers have high levels of expression of the COX-2 enzyme, which is blocked by aspirin. Individuals who regularly used aspirin over a course of several years demonstrated a 36% decrease in the risk of developing one of these high COX-2 expressing colon cancers. These results again demonstrated that drugs that block COX-2 can decrease the risk of colon cancer, and demonstrated that such drugs specifically target those individuals whose tumor development is encouraged by the action of the COX-2 enzyme._

Dr. Markowitz' accompanying editorial maps out those studies which will be required to determine the potential use of aspirin in prevention of colon cancer and to determine which individuals might benefit most from taking aspirin or aspirin-like drugs (NSAIDS) such as ibuprofen and Celebrex. Finally, the editorial outlines potential targets for development of drugs that might provide similar protection as aspirin or COX-2 inhibitor drugs for developing colon cancer but with a lesser risk of adverse side effects.

"Interventional trials have shown a decreased risk of the development of colon cancer in high-risk subjects who were given aspirin or COX-2 selective NSAID inhibitors and observational trials have associated a decreased risk of colon cancer with aspirin use," writes Dr. Markowitz in the editorial. "The researchers' findings provide powerful support for the role of COX-2 as a key mediator in the development of colon cancer and now pose questions about the biologic basis and clinical applications of discovering differences that express high or low levels of COX-2."

Dr. Markowitz has done seminal research in the field of colon cancer genetics and prevention. Among his numerous research articles, he published a study on the findings of a new "Celebrex-like" gene that suppresses the grown of colon cancer in the July 2006 issue of Proceedings of the National Academy of Sciences. Dr. Markowitz likens the gene, called 15-PGDH, to a naturally occurring Cox-2 inhibitor such as Celebrex. These findings may lead to the development of a new drug for colon cancer prevention.

"Sandy and his research team have made great strides in colon cancer prevention," says Stanton Gerson, MD, Director of the Ireland Cancer Center at University Hospitals Case Medical Center as well as the Case Comprehensive Cancer Center. "This editorial and all of his proceeding work may have great impact on individuals at high risk for developing this deadly disease."

Regular, long-term aspirin use reduces risk of colorectal cancer

Patients need to talk to their doctor to discuss risks vs. benefits

The use of regular, long-term aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk associated with colorectal cancer, according to a study published in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute. However, the use of aspirin for chemoprevention of colorectal cancer may require using the drug at doses that are higher than recommended over a long period of time, which may cause serious side effects including gastrointestinal bleeding.

“While the results of our study show that aspirin should not currently be recommended for the chemoprevention of colorectal cancer in a healthy population, there is a need for further studies to help identify for which patients the potential benefits outweigh the risks,” according to Andrew T. Chan, MD, MPH, Massachusetts General Hospital and lead author of the study. “We also need to improve our understanding of how aspirin works to prevent and inhibit the formation of colorectal cancer.”

Study participants were enrolled in the Health Professionals Follow-up Study, a large prospective cohort study which has provided detailed and updated information on aspirin use.

Researchers found that men who used aspirin regularly experienced a significantly lower risk of colorectal cancer, including distal colon cancer, proximal colon cancer and rectal cancer, even after controlling for other risk factors. The reduction in risk was seen in both early (stage I/II) and advanced (stage III/IV) colorectal cancers. There were 975 documented cases of colorectal cancer over 761,757 person-years, among the 47,636 eligible men. Participants who reported regular aspirin use, equal to or more than twice a week, were older, more likely to have smoked, used multivitamins and folate, and consumed slightly more alcohol.

In an average-risk population of men, results showed that the benefit of aspirin was not apparent until after more than five years of use. The greatest reduction in risk was observed at cumulative doses of more than 14 standard tablets (325 mg) per week, which is higher than normally recommended. The benefit of aspirin use appears to diminish less than four years after stopping use and is not evident after four to five years of discontinued use.

The Health Professionals Follow-up Study has been conducted on 51,529 U.S. male dentists, optometrists, osteopaths, podiatrists, pharmacists and veterinarians, who returned a mailed health questionnaire in 1986. The questionnaire included questions about diet, aspirin use and medical diagnoses, including cancer. The biennial questionnaires ask for updated information including cancer diagnoses and aspirin use. The participants were between 40 and 75 years of age when the study began.

This year an estimated 147,000 Americans will be diagnosed with colorectal cancer and 56,500 will die from this disease, with an approximate 1-in-18 lifetime probability of developing colorectal cancer.

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