The Abramson Cancer Center of the University of Pennsylvania
Last Modified: January 6, 2002
Volume 2, Issue 1
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.
Another year has passed us by and March is just around the corner. The NCCRA is preparing to use National Colorectal Cancer Month to raise awareness of this deadly, but often preventable cancer. Once again, the Alliance will distribute several million free educational brochures to community pharmacies across the nation. These same pharmacies will accept $1 donations from customers to raise money for colorectal cancer research. In addition, Katie Couric will do a three part series about colorectal cancer on The Today Show sometime in March. Check the NCCRA's website for updates.
Colorectal cancers are some of the most common cancers in industrialized countries. In 2001, there were an estimated 135,400 new cases and 56,700 deaths in the United States. Approximately 10 to 15% of cases may be caused by genetic abnormalities that run in families. There are two major types of hereditary disorders that lead to colorectal cancers, familial adenomatous polyposis (also known as FAP) and hereditary non-polyposis colorectal cancer (HNPCC). HNPCC accounts for about 5 to 10% of all colorectal cancers, while FAP cases make up only about 1%. In this issue of eNews, we will discuss HNPCC; FAP will be discussed in a future issue.
Dr. Henry Lynch first described HNPCC and the disorder is often referred to as Lynch Syndrome. He further specified that families either had Lynch type I (also called HNPCC type A) or Lynch type II (also called HNPCC type B). Families with Lynch type I often report numerous cases of colorectal cancers in young (under age 50) relatives. The average age of diagnosis of cancer in patients with this syndrome is 44 years old, as compared to 64 years old in people without the syndrome (which is often referred to as a sporadic cancer). Families with the Lynch II syndrome will also report colorectal cancers in young relatives, but will also have cases of "HNPCC related cancers". These related cancers include breast, endometrial, gastric, ovarian, and ureter.
Although many patients may have similar family histories, specific criteria must be met and certain genetic abnormalities must be present for a family to be classified as HNPCC. The genes that have been identified as responsible for HNPCC are MSH1, MSH2, PMS1, and PMS2. Individuals with a mutation in any one of these genes have an estimated 80% lifetime risk of developing colon cancer. People with HNPCC are most likely to develop cancer on the right side of the colon, unlike most sporadic cases, which develop on the left side of the colon. Flexible sigmoidoscopy, a standard screening test for colorectal cancer, only examines the left side of the colon, and is a poor screening test for this population. While people with HNPCC develop polyps at the same rate as other people, these polyps are more likely to progress to cancer. In addition, the progression of polyps to cancer occurs in a shorter period of time compared to sporadic cases on colorectal cancer.
In order to better define families with HNPCC, a panel of experts met in 1990 in Amsterdam to develop criteria for the syndrome, often referred to as the Amsterdam criteria. In the years following this meeting, genetic testing became more readily available and a number of families have been found to carry one of the genetic abnormalities, but do not fit the original criteria. For this reason, in 1999, the Amsterdam criteria II were developed, and now serve as the necessary criteria for HNPCC families.
The criteria are:
Families with histories meeting the criteria may wish to undergo genetic testing to determine if they carry the defective gene. If this test is positive (usually done on the affected family member's tumor) for a genetic abnormality, other family members at risk can then be tested for the same abnormality. If no abnormality is detected in the family member's tumor, then testing other family members would not be informative. However, the tests that are currently available are not 100% accurate. Depending on the methods used, they can miss positive cases anywhere from 5 to 50% of the time. A family may carry a mutation in a gene that has not yet been discovered or a mutation for which that testing has not yet been developed.
Genetic testing is something that should not be taken lightly. One must consider the effect of the outcome of the test not only on themselves, but also in other family members. Concerns may include the availability, or lack of preventive options, passing the gene on to one's children, and discrimination in employment and insurance matters. To assist in this difficult decision, a genetic counselor should meet with anyone wishing to undergo testing. These professionals are trained to help patients understand the issues surrounding genetic testing, and help them make the right decision for them and their family.
People with HNPCC tend to develop cancers earlier than the general population, and therefore should begin screening earlier. It is estimated that 15% of people with HNPCC will develop colorectal cancer by age 40. People with HNPCC should have a colonoscopy beginning at age 20 to 25 years, and repeated every 1 to 2 years. Women in these families are at increased risk for endometrial cancer, and should consider annual transvaginal ultrasound or endometrial biopsy starting at age 25 to 35.
Scientists have learned a great deal about genetic syndromes in the past 10 years. This is, in part, due to the involvement of patients in research studies. If you have a family history of cancer and would like to learn more about cancer risk and research, check out the links below.
American Cancer Society, 2001 Statistics.
CancerNet, A service of the National Cancer Institute. Genetics, Causes, Risk Factors, Prevention of Colon and Rectal Cancer.
Lenhard, R. E., Osteen, R. T., & Gansler, T. (Eds.): The American Cancer Society's Clinical Oncology (2001). The American Cancer Society, Atlanta, Georgia.
Vasen HF, Watson P, Mecklin JP, et al.: New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 116(6): 1453-1456, 1999.
Yarbro, C. H., Frogge, M. H., Goodman, M., & Groenwald, S. L. (Eds.): Cancer Nursing: Principles and Practice (2001). Jones and Bartlett Publishers, Boston, Massachusetts.
Dear OncoLink "Ask The Experts,"
I have just learned that a lot of our family members are carriers of Lynch Syndrome. I have looked everywhere and can't find anything on it. Is there anything you can tell us? I am told it is a form of colon cancer. My uncle was just told he is a carrier. Can you help me?
Timothy C. Hoops, MD, Clinical Assistant Professor of Medicine in the Gastroenterology Division at the University of Pennsylvania and Director of Gastroenterology at Penn Medicine at Radnor, responds:
Lynch Syndrome is one of the inherited syndromes that is characterized by a high risk for the development of colon cancer. Several abnormal genes have been discovered as the culprits for this disease. It is a dominantly inherited syndrome meaning that if the abnormal gene is inherited from the parent, the person will have the disease. If a parent has the disease, there is a 50% chance that they will pass it on to their children. If the parent does not have the disease, it cannot be passed on to the next generation, that is, it doesn't appear to skip generations.
There are other cancers that can occur in Lynch Syndrome, most notably uterine and ovarian cancer in women. The goal in patients who are at risk is to try to prevent these cancers. As such, routine colonoscopic screening examinations are recommended. OncoLink has joined forces with the National Colorectal Research Alliance to help their scientists study the risk factors associated with colorectal cancer and identify potential preventive and treatment therapies. You and your family may be interested in taking our survey. This confidential survey was developed by cancer experts as an interactive way to help our leading scientists study families with a history of colorectal cancer.