Feds Think You Are Too Stupid to Understand Genetic Test Results

Yesterday, the Subcommittee on Oversight and Investigations in the House of Representatives held a hearing during which an apparently damning report on genetic testing by General Accountability Office (GAO), DIRECT-TO-CONSUMER GENETIC TESTS: Misleading Test Results Are Further Complicated by Deceptive Marketing and Other Questionable Practices, was released. For example, the report makes much of the fact that one tested donor who had a pacemaker implanted 13 years ago was told by two of four companies that he was at below average risk for irregular heart beats and two others found his risk to be average. That sounds really bad, doesn't it? Well, maybe not. The GAO report also notes:

Different companies often provide different results for identical DNA: Each donor received risk predictions for the 15 diseases that varied from company to company, demonstrating that identical DNA samples produced contradictory results. Specifically, in reviewing the test results across all four companies for the donors' factual profiles, we found that Donor 1 had contradictory results for 11 diseases, Donor 2 for 9 diseases, Donor 3 for 12 diseases, Donor 4 for 10 diseases, and Donor 5 for 9 diseases….

These contradictions can be attributed in part to the fact that the companies analyzed different genetic "markers" in assessing the donors' risk for disease. As described in a recent article published in the science journal Nature, researchers determine which markers occur more frequently in patients with a specific disease by conducting "genome-wide association studies, which survey hundreds of thousands or millions of markers across control and disease populations."6 DTC companies use these publicly available studies to decide which markers to include in their analyses, but none of the companies we investigated used the exact same markers in its tests. For example, Company 1 looked at 5 risk markers for prostate cancer, while Company 4 looked at 18 risk markers.

I have taken two genotype screening tests from the DTC companies, 23andMe and Pathway Genomics (both of whom sent representatives to testify at yesterday's hearing). Let's take a look at the reported results concerning my risk of prostate cancer. Pathway tests for 18 markers associated with prostate cancer risk and 23andMe tests for 5 such markers. Why the difference? Each company will have different standards for deciding how strongly correlated with prostate cancer risk certain gene variants are. That's a reaonable judgment call, just as any clinician might make. In any case, what are my results?

According to 23andMe, the average risk that men of European ethnicity will get Prostate Cancer between the ages of 35 and 79 is 17.8 out of 100. Based on the markers the company tested, my risk is 15.2 out of 100. 23andMe goes on to tell me:

Assuming the ethnicity setting above is correct, your test results indicate you are not at increased risk for prostate cancer based on genetics. Note, however, that family history, non-genetic factors and genetic factors not covered in this report can also influence your risk for prostate cancer. About one in six men will face this disease at some point in their lifetimes.

Based on the 18 markers tested by Pathway Genomics, the company reported:

You are not susceptible to developing prostate cancer, according to your genetic profile. A healthy diet, routine exercise, and periodic checkups with your doctor will help you stay healthy.

Not diet and exercise again! Anyway, Pathway adds a "genetics overview" which provides the following information about prostate cancer risk:

The identification of genetic markers for prostate cancer is the subject of ongoing research (PMID 19104501). Despite considerable effort, no high risk gene has yet been identified that is specific to prostate cancer (PMID 19005198). Many alleles, however, have been identified which confer small amounts of risk for or protection from prostate cancer; these may be referred to as low risk susceptibility alleles (PMID 19104501). We currently test 18 low risk susceptibility alleles to assess your genetic risk of developing prostate cancer. While most of the low-risk markers were identified from Caucasian populations, one study suggests that their presence in other ethnic populations is likely to predict similar risk or protection (PMID 19318432). On the other hand, some data suggest that there may be some markers that are specific for risk in African-Americans (PMID 17978284).

That doesn't sound very "misleading" to me. By the way, PMIDs are PubMed Identifiers linking customers to various studies on which Pathway is basing its information.

For what it's worth, my prostate-specific antigen test (which I take every year) is through the floor. And at the risk of offering too much information, I do take a daily Avodart pill to treat benign prostatic hyperplasia. Am I going to stop taking the PSA test based on these results? No.

This is early days for genetic testing, and companies are in the process of devising the best ways to use and interpret genetic information. So while I clearly do not believe that I have been "misled" by the DTC companies, are other consumers really likely to be misled by current tests?

Two things to note are: first, so far fewer than 100,000 Americans have used direct-to-consumer gene scanning services; and secondly, early adopters of gene tests pioneer ways to making the information more user friendly for later consumers. And what is the evidence that consumers misunderstand genetic test results? A 2009 study headed up by Colleen McBride from the National Human Genome Research Institute which evaluated the responses of patients who accepted an offer for genetic susceptibility testing for eight different conditions through a health maintenance organization, is somewhat reassuring. The researchers reported, "We found no evidence that those who considered or sought testing were inclined to overestimate the contributions of genetics to common health conditions or to underestimate behavioral risk factors."

Of course, future tests are going to be more accurate, but the way to get there is not by imposing hyper-cautious government, that is, Food and Drug Administration, regulations on the nascent testing industry. That being said, if any companies are engaging in actual fraud they should be punished.

Addendum: For an alternative, and incorrect view of the matter, see bioethicist Arthur Caplan's column here.