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Cancer Health Center

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Cancer Genetics Risk Assessment and Counseling (PDQ®): Genetics - Health Professional Information [NCI] - The Option of Genetic Testing

Table 1. Clinical Utility of Genetic/Genomic Testsa continued...

In summary, genetic education and counseling includes identifying the most informative person in the family to test, which may be an affected family member rather than the individual seeking genetic services. In addition, counseling includes a discussion of the limitations of the test, all possible test outcomes, and the consequences of identifying a variant of unknown clinical significance.[3]

Genetic testing and assisted reproductive technology

Advances in reproductive technology have enabled predisposition cancer genetic testing to be performed in the prenatal setting using chorionic villus sampling and amniocentesis and in the preimplantation setting using preimplantation genetic diagnosis.[4,5,6] A literature review coupled with a brief survey found 55 case reports of prenatal or preimplantation diagnosis performed for cancer predisposition for more than 12 familial cancer syndromes.[4] In a telephone survey of 13 centers listed in an online resource as providing preimplantation genetic diagnosis, nine reported they provided this service for cancer predisposition syndromes.[4]

Reproductive medicine used in the context of predisposition genetic testing for cancer risk raises important ethical, legal, and social issues. A proposed analytic framework recommends considering the following issues:

  1. Does the cancer syndrome include childhood malignancies or significant morbidity or mortality at an early age?
  2. What is the penetrance associated with the gene mutation?
  3. How severe is the syndrome phenotype?
  4. Are there interventions available that decrease the mutation-associated cancer risk or are proven to detect cancer early when it is in a treatable form?[5]

When counseling cancer susceptibility gene mutation carriers who are considering childbearing, it is important to address the issues listed above while maintaining sensitivity to the potential parents' personal beliefs.[5]

Determining the Test to Be Used

Genetic testing is highly specialized. A given test is usually performed in only a small number of laboratories. There are also multiple molecular testing methods available, each with its own indications, costs, strengths, and weaknesses. Depending on the method employed and the extent of the analysis, different tests for the same gene will have varying levels of sensitivity and specificity. Even assuming high analytic validity, genetic heterogeneity makes test selection challenging. A number of different genetic syndromes may underlie the development of a particular cancer type. For example, hereditary colon cancer may be due to familial adenomatous polyposis (FAP), Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, or other syndromes. Each of these has a different genetic basis. In addition, different genes may be responsible for the same condition (e.g., Lynch syndrome can be caused by mutations in one of several mismatch repair [MMR] genes).

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