BUFFALO, NYColorectal cancer is caused by a multistep process,
taking up to 25 years for an adenocarcinoma to develop. This offers
multiple opportunities for prevention strategies to intervene and
decrease the incidence of this disease.
Colorectal cancer is a problem in the developed
worldparticularly the United States, New Zealand, Australia,
Argentina, and Europe, Raymond DuBois, MD, PhD, Minna C.
Wallace Professor of Medicine and Cell Biology, Vanderbilt University
Medical Center, said at the New Horizons in Cancer Prevention
Symposium, hosted by Roswell Park Cancer Institute. It appears
that environment and behavior play critical roles in the development
of this disease.
The potential for a preventive agent to decrease the incidence of
colorectal cancer has already been shown in regular users of aspirin
and other nonsteroidal anti-inflammatory drugs (NSAIDs). There
are multiple epidemiologic studies indicating that people who take
aspirin on a regular basis, for at least 10 years, have a profound
decrease, of almost 50%, in their colorectal cancer risk, Dr.
The proposed mechanism of how aspirin and NSAIDs create antitumor
activity is not completely understood, but one possible mechanism is
their ability to inhibit prostaglandin production. These agents
inhibit cyclooxygenase (COX) activity, which decreases the production
of proinflammatory prostaglandins.
Two COX isoforms have been identified, and most NSAIDs inhibit both.
COX-1 is expressed in many cells, including normal colon tissue.
COX-2 appears to be associated with colorectal adenocarcinomas, in
that more than 80% of colon cancers express COX-2, compared with
normal tissue in the same patient.
This increase in COX-2 in cancerous tissue offers a target in
the cancer cells. We have found that COX-2 upregulation in colon
cancer cells makes the cells resistant to apoptosis. This may explain
why COX-2 increases the neoplastic potential of certain cells,
Dr. DuBois said.
In a recent study, patients with familial adenomatous polyposis (FAP)
who received celecoxib (Celebrex), a COX inhibitor approved for
arthritis, had a 28% decrease in polyp number, a 5% decrease in polyp
size, and a 31% decrease in overall polyp burden, compared with FAP
participants who received a placebo for 6 months (Table).
We need to investigate whether remaining polyps in these
patients changed during celecoxib therapy, Dr. DuBois said,
and to look at how celecoxib affects polyp recurrence and the
long-term effects of this therapy. It is also possible that this
prevention strategy can be applied to other epithelial tumors.