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Current Status of Genetic Testing for Colorectal Cancer Susceptibility

Current Status of Genetic Testing for Colorectal Cancer Susceptibility

Solomon et al have written a valuable primer to guide clinicians in identifying, diagnosing, and treating familial colon cancer syndromes. The authors succinctly describe the essential features of each of the well-defined hereditary colon cancer syndromes, including those associated with colonic adenomas (hereditary nonpolyposis colorectal cancer [HNPCC] and familial adenomatous polyposis [FAP]) and colonic hamartomas (Peutz-Jeghers syndrome, juvenile polyposis, and Cowden syndrome). In addition to the specific features that might trigger recognition of one of these syndromes, we advise health-care providers to consider the possibility of hereditary cancer in cases with the following features:

  • Younger than typical age of onset

  • Autosomal dominant pattern of inheritance

  • Bilateral cancer—ie, in both sides of a paired organ (eg, both breasts)

  • Mulitfocal cancers—ie, multiple separate cancers in the same organ

  • Several relatives with the same or related cancers (eg, colon cancer only or colon and endometrial cancer)

  • Lack of causal environmental risk factors or exposures

The authors make a compelling argument that primary care providers and specialists should be knowledgeable enough about hereditary colon cancer syndromes to recognize or suspect them clinically but that families so affected should almost always be referred to a specialized center for genetic evaluation. Moreover, they describe how genetic counseling covers the spectrum of psychological, ethical, legal, and clinical issues that families face as they try to decide whether to undergo genetic testing as well as the mix of provider skills necessary to deal with these issues. The article highlights the importance of informed consent, which should encompass a thorough discussion of the concerns, expectations, risk perception, and limitations of genetic testing.

Genetic Evaluation

Cancer genetic counselors undergo specialized training in medical genetics, psychology, ethics, medical decision-making, health-care law, and policy as well as the clinical aspects of the hereditary cancer syndromes. They can often provide anticipatory guidance as to how genetic test results may affect medical management and social and family relationships. Few physicians’ offices are staffed to provide this type of care, and there is evidence that genetic test results are commonly misinterpreted.

As described in the article, finding a disease-causing mutation in an affected family member allows genetic testing of at-risk relatives. If a mutation is not identified in an affected individual, further testing of at-risk relatives is not recommended. Any negative test in a family that meets the clinical protégé of one of the familial syndromes could be inconclusive, because the analysis is not capable of detecting all possible mutations in the known genes. Furthermore, a disease-causing mutation could be present in an as yet undiscovered gene. When an affected family member is not available for evaluation, initiating the testing process in at-risk family members can provide only positive or inconclusive results. Clinical diagnosis remains the primary mode of diagnosis for many of these families with hereditary cancer.

Most clinics that specialize in hereditary cancer do not manage the patients on an ongoing basis, but rather, serve as a resource for physicians who are treating patients diagnosed with a hereditary cancer syndrome. Specialized hereditary cancer clinics exist in most regions of the country and can be found online by accessing www.cancer.gov/search/genetics_services/ or www.nsgc.org.

The article provides a valuable resource in its presentation of the guidelines developed by various professional groups to address the appropriate manner in which to offer genetic testing in a clinical setting. Similar guidelines were also recently released in a position statement by the American Gastroenterological Association on Hereditary Colorectal Cancer and Genetic Testing.[1,2]

Medical Management

In addition to genetic counseling, families with a hereditary cancer syndrome often need detailed clinical advice about screening and overall medical care. Each of the hereditary colon cancer syndromes is associated with a unique spectrum of extracolonic cancers, requires a specific screening protocol, and raises difficult medical issues.

For example, women with confirmed or suspected HNPCC require specialized uterine and ovarian cancer screening (endometrial aspirates, transvaginal ultrasound) as well as colonoscopic screening. They may have to make difficult medical decisions concerning whether to undergo subtotal colectomy or prophylactic hysterectomy and oophoerectomy. Individuals with Peutz-Jeghers syndrome may need screening for breast, ovarian, uterine, testicular, or pancreatic cancer plus an upper endoscopy and small bowel evaluation in addition to regular colonoscopy. The combination of highly trained genetic counselors and clinicians with specialized interest and training in hereditary colon cancer can usually address the full spectrum of needs of families with hereditary colon cancer.

Insurance Coverage

Insurance coverage for genetic testing is a complex issue. The combination of expensive genetic tests and concerns about future insurability presents families with difficult decisions. Specialized clinics can work with insurers to help families obtain coverage for genetic testing and for the recommended screening tests. The financial benefits of genetic testing—for example, as seen with the reduced need for screening in at-risk family members who have not inherited the disease-causing mutation—will often convince insurers to cover these services. However, it is sometimes more difficult for insurers to see the logic in covering the costs of recommended screening tests in gene cousins or at-risk family members. When available, outcome data such as those demonstrating the utility of colonoscopic screening in decreasing colon cancer incidence and mortality[3] are particularly useful in convincing insurers to cover these costs. However, many of the screening recommendations for hereditary colon cancer families have not been validated in clinical trials. In such cases, clinics can provide reprints of formal screening recommendations made by various organizations to support insurance coverage.

A portion of a federal law provides protection for group insurance plan holders, stating that genetic information is not considered a preexisting condition unless there has been a diagnosis related to the genetic information. Many states also have laws that protect genetic information. A good resource for state health information can be found at www.statehealthfacts.kff.org.


1. Giardiello FM, Brensinger JD, Petersen GM: AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology 121:198-213, 2001.

2. American Gastroenterological Association Medical Position Statement: Hereditary colorectal cancer and genetic testing. Gastroenterology 121:195-197, 2001.

3. Jarvinen HJ, Aarnio M, Mustonen H, et al: Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118:829-834, 2000.

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