CommentaryGenomic Testing

Bioethical and Clinical Dilemmas of Direct-to-Consumer Personal Genomic Testing: The Problem of Misattributed Equivalence

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Science Translational Medicine  03 Feb 2010:
Vol. 2, Issue 17, pp. 17cm5
DOI: 10.1126/scitranslmed.3000214


  • Fig. 1. Family history and DTC genomic test results for a hypothetical patient, Betty.

    (A) Betty’s three-generation family history. Symbols representing women with cancer are shaded blue. The age of cancer onset is shown in each case. (B) Betty’s personal genomic scanning report about cancer risk and the likelihood of a nonmedical trait, a heightened ability to detect bitter taste. According to the DTC testing company, the chart shows the effects of Betty’s genotype at the eight tested markers. Orange bars indicate increased risk relative to the average, whereas blue bars indicate decreased risk. The light gray bars show the maximum possible effects of all possible genotypes at each marker.



  • Table 1. Differences between high-penetrance Mendelian gene mutations and SNPs analyzed by DTC genomic testing.

    RR, relative risk (relative risk of developing a disease in a given population); CLIA, Clinical Laboratory Improvement Act; CAP, College of American Pathologists.

    High-penetrance mutationsDTC trait-associated SNPs
    Proportion of disease due to mutations or variantsHigh (typically >70%)Low (1 to 3%)
    Attributable risksHigh (RR > 2, typically RR > 10)Low (RR, 1.01 to 1.3)
    Analytic validityClose to 100% (for laboratories with CLIA certification and CAP accreditation)Variable
    Clinical validityFound with high probability in individuals with disease; never or rarely found in normal individualsSame SNPs found in individuals with disease or trait and in controls (but in different proportions)
    Clinical utilityUsed as molecular diagnostic and as predictive testTypically not clinically useful
    ActionabilityOften changes or informs medical management, such as indicating organ-specific surveillanceNot actionable; attributable risks are too low
  • Table 2. Possible scenario for a hypothetical patient, Betty.

    BettyA 40-year-old healthy black woman who comes to her physician’s office with her mother. She is married and has three daughters. She has no complaints.
    Betty’s physicianCompletes Betty’s personal medical history and takes a three-generation family health history (Fig. 1A). Based on her family history, Betty’s physician believes that her family may have HBOC as a result of germline mutations in BRCA1/2. He explains this to Betty and her mother and refers both to a cancer genetics professional.
    BettyRefuses because she has had DTC genomic testing and the test says she is at low risk for several cancers (Fig. 1B). Seven years later, Betty develops metastatic ovarian cancer and dies, despite standard chemotherapy.
    Alternative course of events with improved outcomeBetty and her affected mother (Fig. 1A) should have consulted with a cancer genetics professional, and in the setting of genetic counseling, the mother (who is a living family member affected with a component cancer and therefore the most informative person to test) should have been offered BRCA1/2 testing, including testing for large deletions and rearrangements in these genes (as there is a higher likelihood of these mutations in black individuals with HBOC). If a family-specific mutation was found in the mother, Betty could have been offered predictive testing for the single-site family-specific mutation in the setting of genetic counseling. If Betty were found to carry the mutation, then she could either receive high-risk breast screening (including breast magnetic resonance imaging) or prophylactic bilateral mastectomy; she also could have received prophylactic removal of the ovaries and uterus, which currently is the only intervention shown to save lives from BRCA1/2-related ovarian cancer. Knowing that Betty has a germline BRCA1/2 mutation could have led her physicians to treat her with poly(ADP-ribose) polymerase inhibitors, which have been shown to be highly effective in treating BRCA1/2-related cancers that have metastasized, rather than standard chemotherapy (18).

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