OncoLink eNews: On the Forefront of Colorectal Cancer, Fall 2001

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The Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 21, 2001

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OncoLink would like to recognize the contribution of the National Colorectal Cancer Research Alliance (NCCRA) whose initiative with Pharmacia Oncology and Pfizer has made this publication possible.

Volume 1, Issue 2
Fall 2001


A study published in the August 23rd issue of The New England Journal of Medicine supports the National Colorectal Cancer Research Alliance's (NCCRA) call for colonoscopy to be recognized as the best screening method for colon cancer. The study, conducted at 13 Veterans Affairs medical centers, examined the sensitivity of the nationally recommended screening tests, sigmoidoscopy and fecal occult blood testing (FOBT). A total of 2885 asymptomatic patients, ages 50 to 75 years, performed three FOB tests and then underwent a complete colonoscopy. Researchers noted what would have been found on sigmoidoscopy, as well as what would have been missed with this exam.

The study found that screening with both FOBT and sigmoidoscopy identified only 76% of the advanced neoplasms present in the study population. Another 24%, discovered with colonoscopy, would have been missed with traditional screening methods.

In response to these findings, NCCRA co-founder Katie Couric released this statement: "Our message has always been that colonoscopy is the gold standard for colorectal cancer screening, and this research supports that fact. Knowledge about the disease and your own personal risk is the best tool in the fight against colon cancer. But, finding polyps and removing them isn't the end of the battle-continuing education is a key component in the fight."

The NCCRA is dedicated to the eradication of colon cancer through education, fundraising, research, and early medical screening. Research supported by the NCCRA is looking at the prevention of colon cancer. Areas being studied include finding appropriate genetic markers to identify high risk populations and the use of aspirin like compounds to prevent the formation of polyps. To learn more about colorectal cancer or ongoing studies, call the NCCRA clinical trials resource center at 1-866-724-4100.

Update on the NCCRA/OncoLink Registry

The NCCRA/OncoLink registry has now been accessible online or via the clinical trials call center since March of this year. As of September 1st, 1137 surveys have been completed. Of these, 89% were completed online at OncoLink.

Researchers at Case Western University and Pharmacia have begun contacting people who meet the criteria for their clinical trials. Case Western researchers are looking at families with a history of early-onset breast and colon cancer. Pharmacia is conducting prevention trials utilizing aspirin like compounds.

Potential participants can help by taking the confidential survey, which was developed by cancer experts as an interactive way to help NCCRA scientists study families with a history of colorectal cancer. After completing the survey, the information is entered into a national registry. NCCRA scientists will use the information to determine eligibility for clinical trials investigating prevention and treatment of colorectal cancer. If eligible, participants will be contacted directly by NCCRA research scientists.

The registry survey can be completed by calling the NCCRA Clinical Trials Resource Center at 1-866-724-4100 or complete the survey online.

Ask the Experts

Dear OncoLink "Ask the Experts,"
Can you give me any information on the "virtual colonoscopy"?

Richard Whittington, MD, Associate Professor of Radiation Oncology at the University of Pennsylvania School of Medicine, responds:

Virtual colonoscopy is currently being developed. It is a series of ultra thin CT scan images that are stacked by a computer and then the large intestine is isolated. It is currently investigational, as the early data from a few centers has suggested that it may be nearly as effective in their hands as conventional colonoscopy. It is time consuming since it may involve 100 to 250 CT slices, and the images need to be manipulated after they are obtained. In institutions that do these studies, the patients currently undergo conventional colonoscopy as well to determine the accuracy of the virtual study. All of the centers doing the study have shown that there is a very steep learning curve. The test is least sensitive in detecting villous adenomas, and they are the polyps most likely to contain cancers. It is still necessary to take the bowel prep; only it needs to be more effective than is needed for colonoscopy. Also, due to its experimental nature, insurance companies may not currently reimburse the procedure.

Book Review: "Don't Die of Embarrassment: Life After Colostomy and Other Adventures"

Reviewed by: James Metz, MD

Barbara Barrie is an accomplished actress who received an Academy Award nomination for best actress in Breaking Away and a Tony nomination for her role in Companion. She also starred in the television comedy Barney Miller and the current hit show Suddenly Susan. Barbara Barrie began writing Don't Die of Embarrassment after she was diagnosed with rectal cancer in 1994 while acting in the television mini-series Scarlett.

Don't Die of Embarrassment takes the reader through Barbara's journey of symptoms, diagnosis, surgery, radiation therapy, chemotherapy, and life with a colostomy. It is a candid view of experiences with her family, friends, and the medical profession. The ups and downs of living with a colostomy are discussed from a very personal viewpoint. The book helps the reader to understand the emotional roller coaster cancer patients' experience. It is an excellent book for the medical professional dealing with cancer in any capacity. The book addresses some of the verbal and nonverbal cues' patients pick up from medical professionals that can cause substantial anxiety.

The book is well written, touching, and witty. Not only those people diagnosed with colorectal cancer will benefit from this book, but anyone who has friends or family with colorectal cancer or a colostomy. It is highly recommended by Oncolink.

What You Should Know About Colorectal Cancer

  • Colorectal cancer is the second most common cause of cancer death in the United States.
  • More Americans die each year from colorectal cancer than from breast cancer or AIDS.
  • 156,000 Americans will be diagnosed this year with colorectal cancer and 57,000 will die from the disease.
  • Up to 2/3 of those deaths are preventable with simple screening and prevention methods.
  • Most colon cancers begin as benign polyps, and cancer can be prevented by removal of the polyps.
  • Men and women are equally at risk for colorectal cancer.
  • The older you are, the higher your risk; nevertheless, 13,000 cases will still be diagnosed in people under 50.
  • For most Americans, standard screening with sigmoidoscopy and checking the stool for blood should begin at age 50.
  • Those with a family history of colorectal cancer or polyps or a personal history of inflammatory bowel disease (Crohn's disease or ulcerative colitis), polyps or colon cancer are at higher risk and should consult their doctor to determine when and how to screen.
  • Colorectal cancer is most curable when found before it causes symptoms. More than 90% of colorectal cancers can be cured when caught in their earliest stages.
  • When symptoms are present, the cancer may still be curable if not ignored. Symptoms include: rectal bleeding or blood in the stool, a change in bowel habits, persistent abdominal cramps, chronic diarrhea or constipation, and/or unusual fatigue.
  • Regular exercise and a diet rich in vegetables, fruits and high fiber foods as well as adequate intake of folic acid and calcium may help to prevent colorectal cancer but are no substitute for regular screening.

NCCRA Researcher Sandford Markowitz, MD, PhD, Searches for New Genes Involved in Familial Colorectal Cancer Risk

By: Kristine M. Connor

For Dr. Sandford Markowitz, Ingalls Professor of Cancer Genetics at University Hospitals of Cleveland and Case Western Reserve University and a Howard Hughes Medical Institute researcher, the greatest benefit of being part of the National Colorectal Cancer Research Alliance is the efficiency with which he has been able to locate families with a history of colorectal cancer for his research. Before Katie Couric and Lilly Tartikoff's NCCRA came along, he said, this was "very, very difficult to do."

"One investigator could never accomplish the same level of participation by placing ads or recruiting patients locally," Markowitz said. "Getting assistance from such a national organization to reach a broad national audience-well, you just can't buy that."

In fact, the 250 families now taking part in Dr. Markowitz's "Parent and Sibling Genetic Risk Study"-a study of individuals with two immediate relatives who have had colon cancer or precancerous polpys-were identified as a result of Katie Couric's initial broadcast of the NCCRA's toll-free phone number during the Today show. That broadcast generated as many as 5,000 to 6,000 phone calls from people who were interested in participating, he noted.

This current work is focusing on finding the genetic factors that put some families at higher risk for developing colon cancer. Dr. Markowitz noted that these are not families with the well-established syndromes such as Familial Adenomatous Polyposis (FAP) and Hereditary Non-Polyposis Colon Cancer (HNPCC), in which the lifetime risk of developing colon cancer can be as high as 80 or 90 percent. Instead, he's now concerned with families in which fewer people are developing colon cancer. Even having just one or two immediate relatives who develop the disease or its precursor, colorectal polyps, has been shown to increase a person's lifetime risk.

"We know there is a substantial familial component with this disease," said Dr. Markowitz. "So, we're trying to identify what's going on in these families, and trying to figure out what genetic clues can tell us about risk and who we need to focus on"-besides those families with the more obvious syndromes such as HNPCC and FAP, which involve what Dr. Markowitz called "highly penetrant" genes.

"What we're looking for are genes that are more 'normal' to everyday life," he added. "These are probably more important on a population basis, and ones that tend to work on folks who are a little bit older."

Markowitz and his team are now examining different genes in these individuals to determine which may play a critical role in colon cancer formation. Recently, they won the privilege of having samples analyzed at the National Institutes of Health Center for Inherited Disease Research, which possesses automated gene analysis machines. The equipment makes it possible to look at 300 areas of the gene sequence all at once, which should greatly accelerate the pace of this work.

Finding the genes that are involved can serve many purposes. First, said Markowitz, you can figure out who is at risk for genetic reasons so that they can modify their lives accordingly, such as by having more frequent screenings. Furthermore, the gene might be able to help you find new targets for treatment and even for prevention, if it suggests that environmental or lifestyle factors, such as too much fat in the diet, are also involved.

As indicated on the NCCRA Web site, Markowitz and his colleagues are still seeking people with two immediate relatives (a parent, a child or a sibling) who have had colon cancer, with one of those two immediate relatives being under the age of 65. They are also looking for patients with one immediate relative (a parent, a child, or a sibling) who has had colon cancer and was less than 50 years of age when they were diagnosed with the disease. He and NCCRA colleague Dr. Bert Vogelstein, who is involved in similar research, screen all questionnaires submitted in order to find families who meet this criteria.

Markowitz said that he sees this research as a natural progression of work he has already done to better understand the genetics of colon cancer. For example, he and his colleagues have already discovered that two key pathways-one that governs cell growth and the other that maintains the integrity of colon cell DNA-are often inactivated in people who develop colon cancer. They found that a breakdown in the DNA mismatch repair mechanism played an important role not only in cancers related to the HNPCC family syndrome, but also in a portion of sporadic cancers (those without an obvious familial component) in the general population. They also found that, in many of these repair-deficient cancers, a genetic mutation interferes with the shedding of cells that line the colon that would normally take place.

Dr. Markowitz said he is hopeful that all of his work will move toward clinical applications. Ultimately, he would like to find a way to use these and other genetic clues to develop a much simpler screening test, ideally a blood test, for colorectal cancer.

Like the participants in his research, he knows firsthand the impact that colon cancer can have on a family. His own father was diagnosed while Markowitz was completing his training as an oncologist, and this helped propel him to become part of the effort to better understand the disease.

"Certainly this is a disease I would like to make an impact in," he said. "I appreciate the responsibility I've been given by organizations like the NCCRA and the Howard Hughes Medical Institute, and I plan to honor it."

OncoLink eNews: Colon On the Forefront of Colorectal Cancer is published quarterly and contains articles written by doctors, nurses, researchers, and patients. It reports on current developments in colorectal cancer research, prevention, risk, and treatment. Please feel free to review articles online.


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