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The genetics of colorectal cancer


A 52-year-old patient arrives at the busy family practice office where you work for his follow-up visit. He had not undergone colon cancer screening, despite his age, but agreed to have a colonoscopy. When the results were faxed to your office, you were shocked to learn that he has Stage I colon cancer. He is returning to the office to discuss the finding, obtain referrals to appropriate specialists, and determine a plan of care. You plan to discuss additional testing with him. How does genetic testing apply to this situation?

A 45-year-old woman is being seen in your office for the first time. As you take her family history, you note that her mother was diagnosed at age 53 with colorectal cancer, and died at age 65 from metastatic disease. Your patient has never had a colonoscopy or other screening exam for colorectal cancer. What will you tell this patient about colorectal cancer screening?

Colorectal cancer (CRC) is the third most common cancer, and the third most common cause of deaths from cancer, in the United States. The National Cancer Institute estimated that there would be approximately 142,500 new cases of CRC, and approximately 51,000 deaths from CRC in 2010.

Recent recommendations highlight the importance of tumor genetic testing for all newly diagnosed CRC patients, and of screening in individuals with a family history of CRC. This article will review what you need to know to help patients like the two described in the above scenarios.

Persons newly diagnosed with CRC (first scenario)

In 2009, the independent, non-federal Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working Group recommended genetic testing of the tumors of all newly diagnosed CRC patients, regardless of family history. This is because 2% to 4% of CRC patients will have an inherited syndrome called Lynch syndrome, which is caused by specific genetic mutations, and affects males and females equally. These mutations significantly increase risk for CRC before age 70 (45% for men, and 35% for women), and for second primary CRC (16% within 10 years). Persons who carry these mutations have Lynch syndrome, whether or not CRC is present. Lynch syndrome is Autosomal Dominant, which means that people who carry the mutation have a 50% chance of passing it along with each pregnancy.

EGAPP recommended preliminary and diagnostic testing for Lynch syndrome. Preliminary testing including microsatellite instability (MSI) or immunohistochemistry (IHC) testing, and testing for mutations in the BRAF gene determines whether patients should undergo diagnostic testing. Diagnostic DNA testing involves sequencing the genes involved in Lynch syndrome, which are called mismatch repair (MMR) genes. Mutations in 4 MMR genes are commonly associated with Lynch syndrome: MLH1, MSH2, MSH6 and PMS2. See below for more information about these tests.

Testing Table

This recommendation represents a significant shift in tumor and genetic testing protocols for CRC patients. Testing protocols for family members of CRC patients will also change: identifying Lynch syndrome mutations in CRC patients allows family members to be tested for the mutation. Family members who carry the MMR mutation should have colonoscopy screening earlier and more frequently than the general population. By targeting these high-risk family members, the low (<50%) screening rates of relatives of CRC patients, and their overall health and well-being, may be improved.

Nurses need to be aware of the recommendation for genetic testing of the tumors of all newly diagnosed CRC patients, like the patient the first case scenario. Because that patient has been diagnosed with Stage I colon cancer, his plan of care should include preliminary testing of his tumor tissue and/or diagnostic sequencing of his DNA. Whether one or both of these options is pursued would depend on the treatment plan, and whether tumor tissue will be available for preliminary testing. How testing would proceed for this patient will vary depending on the facility where he is receiving care: since these recommendations are so new, not all facilities will have implemented testing protocols yet.

Nurses can work collaboratively with other healthcare providers in their institutions, to ensure appropriate information is offered to newly diagnosed CRC patients. Regardless of specific institutional approaches to information provision and testing for Lynch syndrome, nurses are likely to be approached with questions about this testing, and can serve as a valuable source of information for patients and families. Nurses aware of institutional or clinic protocols for referral of patients for genetic education and counseling can involve genetic health care providers when the diagnosis of Lynch syndrome is suspected. Nurses could also provide valuable education for the public, by creating informational bulletin boards or pamphlets for use in offices or on patient care units.

Information for health care providers on the EGAPP guidelines is available at:

and information specific to the tumor genetic testing recommendations is available at

Information for the general public on the EGAPP guidelines is available at

Family history of CRC: When the MMR mutation status of family member diagnosed with CRC is unknown (second scenario)

Because the recommendations for tumor genetic testing are so new, and represent a change in care of CRC patients, you will encounter patients with a family history of CRC, but with no information on whether the CRC patient has Lynch syndrome, as in the second case scenario.

Family members of CRC patients have increased risks for CRC compared to the general population. The patient described in the second case scenario is a good example of someone whose family history puts her at increased risk for CRC. CRC screening recommendations have been issued for the general population and for people at increased risk. Asymptomatic adults over age 50 who are not at high risk for CRC have multiple options for screening, and should consult with their health care providers to make an appropriate choice. Individuals at increased risk of CRC should follow more stringent recommendations. Increased risk includes a personal history of polyps or CRC, a family history of CRC or polyps, a genetic condition in the family or a diagnosis of inflammatory bowel disease. This review focuses on persons at increased risk due to a family history of CRC or polyps. Recommendations for patients at average risk or in the other high-risk categories can be found in the article by Levin and colleagues.

When you learn your patient has a family history of CRC or polyps, as in the second scenario, find out as much detail as possible, including which family members were diagnosed, and at what age. According to the genetic/genomic nursing competencies, all professional nurses should be able to complete a three-generation family health history; including information on CRC and polyp diagnoses in the family will help assign appropriate risk status, screening recommendations and indications for referral to a genetic healthcare professional. See the table below for more information.

Table 2

These recommendations may come as a surprise to your patients, particularly for those who have a relative with colorectal polyps, not cancer. The recommendations are designed to begin screening early enough to find and remove premalignant lesions before they become cancerous. One of the biggest benefits of screening for CRC is the ability to actually prevent the development of cancer. The potential health and economic benefits of ensuring appropriate screening participation are enormous, but can only be realized with recognition of the need for participation in CRC screening.

More information on family history, including links for families to document their own family health histories, is available at http://www.cdc.gov/genomics/famhistory/index.htm.

Nurse’s role

Nurses play a key role in providing care to newly diagnosed CRC patients, and to those with a family history of CRC. Nurses should recognize symptoms associated with possible CRC, including: change in bowel habits such as diarrhea and constipation; change in stool characteristics (for example, stools that are thinner than usual); signs of rectal bleeding or blood in the stool (for example, dark or tarry stool, bloody streaks, frank blood); persistent abdominal discomfort such as cramping, gas, or pain; feeling that the bowel does not empty completely; weakness or fatigue; loss of appetite; and unexplained weight loss or anemia. Be aware that CRC (and particularly early-stage CRC) does not necessarily cause recognizable symptoms, highlighting the importance of access to screening tests for all patients. See the below for more information about nursing interventions.

Nursing Interventions

Nurses make a difference

Nurses who keep up with new and revised recommendations for patient care and testing, such as tumor genetic testing and family history documentation, can advocate for patient access to these. Nurses also can take time to educate and inform CRC patients and their families of the options available to them. Through their actions, nurses can promote early identification and reduce mortality from CRC.

Anne L. Ersig, PhD, PNP-BC, is an assistant professor, in the college of nursing at the University of Iowa, Iowa City.


U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2007 Incidence and Mortality Web-based Report. 2010; www.cdc.gov/uscs. Accessed December 27, 2010.

National Cancer Institute. Colon and Rectal Cancer. 2010; http://www.cancer.gov/cancertopics/types/colon-and-rectal. Accessed December 27, 2010.

Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med. 2009;11(1):35-41.

Palomaki G, McClain M, Melillo S, Hampel H, Thibodeau S. EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med. 2009;11(1):42-65.

Fletcher R, Lobb R, Bauer M, et al. Screening patients with a family history of colorectal cancer. Journal of general internal medicine. 2007;22(4):508-513.

Levin B, Lieberman DA, McFarland B, et al. Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline From the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology. 2008;134:1570-1595.

Consensus Panel on Genetic/Genomic Nursing Competencies. Genetic and Genomic Nursing: Competencies, Curricula Guidelines and Outcome Indicators (2nd edition). 2009; http://www.genome.gov/27527634.

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