Genetic Screening for Colorectal Cancer

Megan A. Jaskowiak

Copyright 1999


Due to the human genome project and other genetic research, tests for mutation which cause diseases have been developed. The list of these illnesses include several types of cancer. Doctors have estimated that as many as 3,000 diseases are due to mutations in the genome. These diseases include several types of colon cancer in which three different genetic tests have been already developed. Debates have arisen on whether these tests should be used regularly or not. Questions including the patients= rights of privacy and the possibility of loss of health or life insurance have been argued over in both the media and political arena.

Colon cancer develops in the part of the gastrointestinal tract that absorbs water and minerals before waste products are disposed via the rectum. In women endometrial cancer is related to colon cancer. This type of cancer is the second leading cause of death due to cancer in the United States. Over one-hundred fifty thousand individuals will be diagnosed this year and this cancer will probably be responsible for about 47,900 deaths in 1999 ( Most colon cancers are adenocarcinomas that develop from the glandular cells. Ninety percent of all colon cancer cases will develop in individuals after 50 years of age. Ninety percent of all tumors arise from polyps that are commonly found in people older than 50. Prevention includes regular exercise and a diet high in fiber. The most important risk factor is age. Medical screening includes a yearly blood occult test after age 50 and a colonoscopy every 3 years after age 50. Regular screening detects polyps that have become precancerous. If regular screening is not done, the cancer is not detected until blood is found in the feces or other symptoms appear including intestinal blockage. By this time the tumor has developed and a section of the colon must be removed. Only 37% of all colon cancers are found in the early stages of the disease. This cancer can easily move and form colony tumors in other organs. After this occurs, the survivorship drops drastically. Less than 10% of colon cancers are caused by inherited gene mutations in which tests have been designed.

The genetic tests developed for colon cancer include hereditary nonpolypsis colon cancer (HNPCC), familial adenomatous polyposis (FAP), and a mutation related to FAP that is only found in Jews of Eastern European descent. These two types of colon cancer are among the rarest types of colon cancer HNPCC has only a few polyps present or occasionally no polyps are present. In HNPCC, colorectal cancer occurs primarily on the right side of the colon whereas most sporadic colon cancer is left-sided. The chance of developing other cancers increases with HNPCC. These include uterus, ovary, stomach, urinary tract, small bowel, and bile ducts. Another name for HNPCC is Lynch=s syndrome. If a person is positive for the genetic test, they are 85% likely to develop cancer.

This type of colon cancer is caused by a mutation in the DNA mismatch repair (MR) system (O=Leary, 1999). During the process of replication, if errors are not repaired by the 3' to 5' exonuclease activity of DNA polymerase, then they are corrected by the MR system. Six genes are involved in the MR system. HHNPC develops when one of two of these genes are mutated. Many mutations in these two genes have been detected. This mutation is autosomal dominant which means that a person whose parent has the mutation, the person has a 50% chance of having the mutation.

FAP is the rarest of all types of colon cancer. It accounts for less than 1% of all colon cancer diagnosed a year. 100 to 1000s of polyps develop in the lower colon. These polyps begin to appear in teenage years. Cancer develops in one of these polyps usually before 50 years of age. If a person test positive for this mutation, they are 100% likely to develop cancer. Doctors recommend a complete colectemy (removal of the whole colon) when polyps develop. FAP is caused by a mutation in the Adenomatous Polyposis Coli (APC) gene. A related mutation is the APC11307k gene (http:\\ This genetic mutation has only been found in Askenazi Jews (Eastern European descent). This mutation is thought to be found in about 6% of all American Jews. If this is true then this is the most common heritable cancer. This mutation does not have as high a risk factor as FAP; it is only about 35%. This different mutation is in the same gene, but results in an unstable gene instead of a direct mutation. If this instability helps create genetic changes at the spot where the FAP mutation occurs, then cancer will most likely occur. These mutations are also autosomal dominant.

All three of these genetic tested are performed by protein assays. These assays are expensive and take experience to run correctly. The cost of these genetic test will drop if the correct restriction enzymes and nucleic acid probe. So, that the cheaper and quicker restriction fragment lenght polymorphisms can be used (.Biesecker and Garber, 1995).

An ongoing study at Johns Hopkins may have discovered a genetic mutation that will provide a test for most of all colon cancers (Rogers, 1994). They have located a mutation that is present in about 40% of all tumor cells and was found in some control group cells. However, it is unknown now time if this mutation is caused by the cancer or if it is a precursor to the cancer itself. This mutation is what is called loss of imprinting. One set of alleles is provided by each parent. In some genes, the alleles always recognize that they came from the maternal or parental gamete and in these genes only the allele from one parent is turned on. A loss of imprinting will cause a maternal allele to think that it is a paternal allele and vice versa.

So far genetic testing for colon cancer is highly recommended by the medical community for only a few groups of individuals. These groups include Jews of Eastern European descent, people who have three or more first degree relatives who had colon cancer or a person wit one relative who was diagnosed with colon cancer before age 50. Also, if a person develops irritable bowel syndrome or polyps at a young age, genetists recommend the test. However, the genetists recommend extensive genetic counseling before the test. During this counseling a family pedigree will be made to see if one really needs the test. Also, issues such as health insurance and personal history of depression will be talked about before any testing will be done.

If one is positive for any of these mutations, the medical recommendation is one of closely watching for precancerous cells. For FAP, the recommendation is to begin colonoscopys in the late teens and to hold off doing the collectomy until the person is old enough to be part of the surgical decision making. For HNPCC, colonoscopys should begin in the mid20's and have surgery when a precancerous growth is found. Closely watching precancerous cells in ovaries and endometrial tissue is also recommended for women who test positive.

The Pros and Cons of Genetic Screening

Many people feel genetic screening should not become routine and even say people should be discouraged to have them done. Screening for the mutations that cause colon cancer is only beginning to be done outside the research labs. Many issues must be resolved before genetic screening becomes as routine as cholesterol tests.

The proponents of genetic testing see a future where genetic testing is as routine as getting your blood pressure checked. They see Internet genetic screening and counseling and a medical field so advanced that pills will all but eliminate your chances of developing the diseases that are the leading causes of death. Already two drugs have been introduced to lower one=s risk of breast cancer (Langreth, 1999). They see only the good that could possibly come from genetic screening.

The medical profession has a different outlook. Genetists and genetic counselors see many obstacles that must be overcome before a future like the one above could truly come about (Biesecker and Garber, 1995). To begin with the public must become much more informed. Even medical doctors whose speciality is not in the field of genetics do not understand the complexities involved in genetic screening. The average American does not understand even the basic genetic principles. Most often an uninformed individual would either blow their personal risk out of proportion or do not take it seriously enough. In a 1999 study, people who had more than one relative who died of colon cancer did not know that they had a higher risk of getting the disease than other people in their same sex, age, ethnicity group. However, these people would undergo genetic testing. Also, many health care providers do not know enough to either to help recommend testing or to refer a patient to a genetic counselor based on a patient=s family history. The medical profession also knows that the issues of cost-effectiveness needs to be solved before tests become more routine especially in the cases of rare mutations such as HNPCC and FAP. However, these setbacks do not dissuade the medical profession from seeing a future where genetic screening is routine.

The medical and scientific communities see the benefits of routine genetic screening. The most obvious benefit is a better opportunity for early diagnosis (Peterson, 1999). Genetic screening and monitoring of people who test positive will allow doctors to study phenotypic and genotypic correlations (Blackburn and Giardiello, 1995). Extensive screening will give them actual case studies of when a cancer causing mutation is activated. If these medical screenings were implemented then the number of colon cancer cases found in the early stages would increase. Also, gene therapies to alter these mutations will be developed in the hopes that it will eliminate the chance of getting the disease all together. Doctors see it as a way they may finally conquer a disease that seems to have no cure.

A moral not ethical issue some people have with genetic screening is its ties with genetic engineering. These individuals feel that if genetic screening becomes routine it will lead to routine gene therapy. In their eyes in a world where gene therapy is an everyday occurrence producing superior children will be deemed okay and birth decisions will be based solely on the genetics of the fetus. Many believe that gene therapy and genetic engineering is only okay if it is to cure a disease. However the major concerns now with genetic screening is the question of who has the right to know the results(Brensinger, 1999). The major problem with genetic screening is one of discrimination. Some worry this will lead to ostersizing people because of diseases they may get (Kinsley, 1997). The possibility of losing one=s insurance or even job is the reason many people refuse to be tested (Jeffrey, 1999). Also, many others are getting tested but refuse to inform their primary care physician or have it entered into their medical records because they fear the possibility of their insurance company getting ahold of the data. The problem boils down to insurance companies ability to charge extra or refuse coverage because of what is known as preexisting condition. For example, a person where a number of family members have died of heart attacks will have to pay extra for individual health care after age 40 or if this person has one heart attack he may be denied coverage. The feeling is that the insurance companies see genetic screening as a new and ultimate detection method for preexisting conditions. So, that someone who has an 80% better chance of getting colon cancer will be denied coverage when they finally develop colon cancer. Many states have passed laws prohibiting discrimination due to genetic test results. Federal laws have been passed. These laws are not very strict and are very open to interpretation. In some states these laws were not passed because of heavy lobbying from insurance groups especially life insurance groups. It is possible that the insurance companies will make it so hard to have insurance that a national healthcare system will be the only option (Hallowell, 1999). Many individuals recognize the possibility of not having insurance cover the expenses of treatment for colon cancer, but they do not often think of life insurance. Colon cancer kills approximately 40,000 people a year. Most of these individuals are between the ages of 50 and 70 and therefore likely to leave behind a family. If one has a family to think of life insuranc is a great concern. Another possible problem that could arise is job discrimination. An employer could possibly not hire someone if they know they will raise the companies insurance rates or they know the person may have to leave the job early for some type of treatment. In a recent interview, nine companies admitted to doing genetic screening of their employees and potential hires (Raab, 1998). They sited reducing illness absenteeism and monitoring effects of chemical as their reasons for the tests.

Another issue in routine genetic testing for colon cancer is the cost of these tests. The genetic tests developed so far for colon cancer only concern the rarest forms of this disease and are not recommended by the medical community for the public. The tests for these genetic mutations are expensive and because of the insurance issue many people are recommended to pay out of pocket and therefore, the number of individuals willing to get the test is limited.

My Opinion Genetic screening is treated like science fiction on both sides. It is seen by the people who are for it as a way of curing the most horrendous diseases. They see a world with genetic screening as one without cancer. On the other hand, the people against testing see a world that has genetic screening as a world where people are discriminated against just because of their possibility of developing a disease and even have abortions done because of the possibility of diseases. Neither side really sees the medical possibilities of routine testing now. Right now the only cure for cancer is early detection and the possibility that the proto-oncogene will be removed from the body. Any way of increasing the chances of early detection should be thought of as good. Insurance companies are only thinking of the future, If genetic screening of curable adult onset disease was routine, they would actually save money. The removal of precancerous cells is much cheaper than the usual run of chemotherapy. For example this is the reason pap smears are now routine and paid for by insurance companies. Most genetic tests are not at the point that they are ready to be routine.

With that said, I do not believe that insurance companies should be allowed to think of genetic mutation as a preexisting condition. Preexisting conditions are highly discriminatory and eliminate the purpose of health insurance. However, there is large difference between the likelihood of someone who has had one heart attack in having another heart attack and the likelihood of someone developing cancer if their gene is mutated.

This is a personal issue with me. Both my paternal and maternal grandmothers died of complications from colon cancer. My father has irritable bowel syndrome and colitis. It is highly unlikely that I would test positive for the rarer types of heritable colon cancer. However, with my family history I would probably want to be tested if they do develop a test for the mutation that may cause 40% of all colon cancers. I think I would want the test. It is a preventable disease. I would know that I need to start getting colonoscopys earlier and more often than the recommended. However, I would not like anyone besides myself, my doctor and maybe my family to know my results of my test. Nothing including a job or insurance should be withheld from a person for some disease they might develop. Also, insurance companies should be happy since a colonoscopy and a small outpatient surgery to remove precancerous polyps would be a lot less expensive than full-blown surgery and six months of chemotherapy. I would not look at it as an early death notice, but as a new type of prevention.


Despite the pictures given in newspaper articles genetic screening has a far way to go before it becomes more routine. The public needs to become more informed about the science of genetics. The tests and the results are difficult to understand without any background in biology. The tests need to be more refined and cost-effective. The population has to decide the importance of these tests and their future effect on the insurance business.


Biesecker, B. B. and J. E. Garber. 1995. Testing and counseling adults for heritable cancer risk. Journal of National Cancer Institute Monographs, 17:115-118.
Blackburn, G. L. and F. M. Giardiello. 1995. Developing strategies for intervention/prevention at risk of hereditary colon cancer. Journal of National Cancer Institute Monographs, 17:107-110.
Brensinger, J. D. 1999. Genetic testing and discrimination: a cause for concern? Mid-Atlantic Cnacer Genetics Network Newsletter. Fall 1999.
Jeffrey, N. A. A change in policy. Wall St Journal. October 18, 1999, p. R15 Hallowell, C. 1999. Playing the odds. Time. January 11, 1999.
Kinsley, M. 1997. Oh, my aching genes! Drawing a tube of blood is just one of many ways to judge people. Time. Sept. 29, 1997.
Langreth, R. 1999. Early warnings. Wall St. Journal. October 18. 1999, p. R7.
National Cancer Institute. Colon and Rectum Cancer.
O’Leary, T. 1999 Molecular diagnosis of hereditary nonpolyposis colorectal cancer. JAMA: Journal of the American Medical Association. 282 (3): 281+.
Peterson, G. M. Lessons from familial cancers. Mid-Atlantic Cancer Genetics Network Newsletter. Fall 1999.
Raab, M. 1998. Genetic shakeup. Working Woman. October 1998.
Rogers, J. 1994. Study shows imprinting directly tied to cancer. Johns Hopkins news press release. June 24.

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