Current Status of Genetic Testing for Colorectal Cancer Susceptibility

February 1, 2002

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:

Solomon et al have written a valuableprimer to guide clinicians in identifying, diagnosing, and treating familialcolon cancer syndromes. The authors succinctly describe the essential featuresof each of the well-defined hereditary colon cancer syndromes, including thoseassociated with colonic adenomas (hereditary nonpolyposis colorectal cancer [HNPCC]and familial adenomatous polyposis [FAP]) and colonic hamartomas (Peutz-Jegherssyndrome, juvenile polyposis, and Cowden syndrome). In addition to the specificfeatures that might trigger recognition of one of these syndromes, we advisehealth-care providers to consider the possibility of hereditary cancer in caseswith 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 thesame organ

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

Lack of causal environmental risk factors or exposures

The authors make a compelling argument that primary careproviders and specialists should be knowledgeable enough about hereditary coloncancer syndromes to recognize or suspect them clinically but that families soaffected should almost always be referred to a specialized center for geneticevaluation. Moreover, they describe how genetic counseling covers the spectrumof psychological, ethical, legal, and clinical issues that families face as theytry to decide whether to undergo genetic testing as well as the mix of providerskills necessary to deal with these issues. The article highlights theimportance of informed consent, which should encompass a thorough discussion ofthe concerns, expectations, risk perception, and limitations of genetic testing.

Genetic Evaluation

Cancer genetic counselors undergo specialized training inmedical 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 mayaffect medical management and social and family relationships. Few physicians’offices are staffed to provide this type of care, and there is evidence thatgenetic test results are commonly misinterpreted.

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

Most clinics that specialize in hereditary cancer do not managethe patients on an ongoing basis, but rather, serve as a resource for physicianswho are treating patients diagnosed with a hereditary cancer syndrome.Specialized hereditary cancer clinics exist in most regions of the country andcan be found online by accessing

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

Medical Management

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

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

Insurance Coverage

Insurance coverage for genetic testing is a complex issue. Thecombination of expensive genetic tests and concerns about future insurabilitypresents families with difficult decisions. Specialized clinics can work withinsurers to help families obtain coverage for genetic testing and for therecommended screening tests. The financial benefits of genetic testing—forexample, as seen with the reduced need for screening in at-risk family memberswho have not inherited the disease-causing mutation—will often convinceinsurers to cover these services. However, it is sometimes more difficult forinsurers to see the logic in covering the costs of recommended screening testsin gene cousins or at-risk family members. When available, outcome data such asthose demonstrating the utility of colonoscopic screening in decreasing coloncancer incidence and mortality[3] are particularly useful in convincing insurersto cover these costs. However, many of the screening recommendations forhereditary colon cancer families have not been validated in clinical trials. Insuch cases, clinics can provide reprints of formal screening recommendationsmade by various organizations to support insurance coverage.

A portion of a federal law provides protection for groupinsurance plan holders, stating that genetic information is not considered apreexisting condition unless there has been a diagnosis related to the geneticinformation. Many states also have laws that protect genetic information. A goodresource for state health information can be found at


1. Giardiello FM, Brensinger JD, Petersen GM: AGA technicalreview on hereditary colorectal cancer and genetic testing. Gastroenterology121:198-213, 2001.

2. American Gastroenterological Association Medical PositionStatement: Hereditary colorectal cancer and genetic testing. Gastroenterology121:195-197, 2001.

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