Research Update: Colon Cancer and Inflammatory Bowel Disease

The Search for Biomarkers

One of the most dreaded complications of IBD is increased risk for colon cancer, a risk that rises after people have had ulcerative colitis or Crohn's disease of the colon for more than 8 to 10 years. Unfortunately, present screening methods, including colonoscopy, are time-consuming, expensive, inconvenient for patients, and not infallible. What's needed is a quick, non-invasive test for colon cancer based on a biomarker, comparable to PSA (prostate specific antigen) for prostate cancer, found by a simple test. Enter CCFA's Biomarkers in Colon Cancer Challenge, a research plan to speed the quest for a colon cancer biomarker.

Assessing Risk

Increased colon cancer risk actually applies to a minority of IBD patients. Fewer than 10% of people with colitis and colon-localized Crohn's disease will ever develop cancer. It is crucial, then, to try to identify the vulnerable minority who need to be screened on a regular basis. In this way, doctors will be able to focus resources on those who need them, allowing the low-risk majority to avoid unnecessary colonoscopies.

What Are Biomarkers?

Biomarkers are measurable substances in the blood, stool, or other parts of the body that indicate the presence of a disease. Unlike colonoscopy, a simple biomarker test would be easy to administer, cost-effective, and highly accurate.

Colonoscopy is not only cumbersome and costly; it isn't even completely effective, for the following reasons:

• Changes in the colon are sometimes invisible to the naked eye during a colonoscopy.

• To achieve the most reliable results, a large number of tissue samples, called biopsies, must be taken during the procedure and examined under a microscope to detect cancerous or precancerous changes.

Even with this rigorous, difficult monitoring process, in the best of hands a number of precancerous changes in the colon can go undetected.

By contrast, if a biomarker is present in a patient's blood, stool, or intestinal lining, it could be used as a complementary test to colonoscopy. Instead of multiple tissue biopsies, a simple blood or stool sample could provide the information a doctor needs to detect malignant changes.

Are There Different Types of Biomarkers?

There are two principal types of biomarkers: immunologic markers and genetic markers.

The first group, immunologic markers, mainly includes antibodies against certain proteins found in cancerous and precancerous cells. When a foreign substance, or antigen, enters the body, specialized immune cells respond by producing antibodies. The presence of antibodies in a person's blood or cells, therefore, is a tip-off that the immune system has mounted a response to a specific antigen.

Although no useful colon cancer-specific antibody has been found yet, researchers have observed a number of proteins in colon cancer that are absent in healthy tissue. A search for antibodies to these proteins, therefore, makes sense.

A second potential group of biomarkers includes proteins or DNA from malignant cells that are subsequently shed into the stool.

Challenges in IBD Research

In 1990, CCFA first issued Challenges in IBD Research – a strategic plan that specified broad goals and a timetable for realizing them. In partnership with some of the world's most distinguished scientists, CCFA identified timely priorities and resources considered essential for advancing the science that will ultimately lead to a cure for IBD. These priorities are reviewed and revised periodically.

Today, Biomarkers in Colon Cancer is one of CCFA's top research Challenges. The Foundation is currently supporting studies to identify a biomarker that is consistently positive in people with malignancies in the colon and consistently negative in the majority of IBD patients with no cellular abnormalities.

A Better Way to Screen

A biomarker test would not only be simpler and less expensive than colonoscopy but more effective as well. For patients with positive test results, it would allow for earlier intervention. A biomarker could also be used to determine whether patients are responding to therapy and improving clinically.

Just as PSA has been a boon to early detection of prostate cancer, so will an immunologic or genetic biomarker boost the early detection of colon cancer in IBD patients, vastly curtailing this deadly complication.

The Main Rationale

Once researchers succeed in identifying and validating a biomarker for colon cancer, it will be used to distinguish between those at risk and those with no signs of malignancy. The at-risk minority will be targeted for attention, while the majority will be spared the need for uncomfortable, time-consuming colonoscopies. Instead, patients will be tested annually for the presence of the biomarker.

Early Results

Early results of the Biomarkers in Colon Cancer initiative have been coming in, principally in the area of genetic testing.

• A group of researchers at the Cleveland Clinic have developed highly promising genetic tests to detect which colitis patients are at risk for colon cancer. However, as yet, no comparable tests have been developed for people with Crohn's disease. The researchers aim to understand more about the role of abnormal and damaged DNA in the progression of colon cancer in patients with colitis. They will also apply a similar approach for detecting cancer in people with Crohn's colitis (Crohn's disease that is localized in the colon).

• Another research team is trying to determine whether the genetic markers seen in stool samples are the same as those found in cells lining the colon in high-risk patients. Tissue samples from biopsies taken during colonoscopies and surgical procedures are being analyzed for biomarkers and compared with biomarkers in stool samples.

• A third group has been testing a set of genetic biomarkers for ulcerative colitis to make sure they are reproducible and highly accurate.

Hopefully, these and other studies soon to be funded under the Challenges umbrella will lead to a new, less invasive approach to managing colon cancer risk in IBD patients.

The Biomarkers in Colon Cancer initiative is already bearing fruit, and the Foundation continues to accept applications for new biomarkers research projects. In this way, CCFA will keep the momentum going until a biomarker is found.