HEALTH POLICY:

SUMMARY: Is genetic screening beneficial to the public? With a few exceptions, it is not yet ready for clinical deployment.

The Human Genome Project was unfortunately often touted as a "magic bullet" that would enable scientists and doctors to predict and prevent many diseases, to an almost science fiction level (later scientists began to appreciate the importance of epigenetics in normal health and disease). Such hype is perhaps best exemplified by shady companies such as 23andMe.

This company sells people personalized health and ancestory genomic tests for several hundred dollars each, and is attracting quite a bit of private investment. The lure of such companies probably lies in the typical person's vision of somehow being in control of his or her own preventive medical care; e.g. "I'm at genetic risk for heart disease, so maybe I should start eating healthier foods."

Sometimes genetic screening is useful. Whether this is true of genetic screening as a whole is another matter altogether.

A report by Wayne Hall (University of Queensland, Australia) and coworkers makes a powerful argument that we should be careful of the hype surrounding genetic screening. With a few exceptions, genomic medicine has not yet reached the point that it is a socially responsible tool for public health screening.

Reasons for skepticism.

Does a typical single genetic test report whether you are likely to eventually develop a disease? The short answer is no, it will not.

Most genetic tests may tell you that you are 1.1 to 1.6 times more likely to develop a particular disease over your lifetime. This is a very small risk, shared with many people the world over.

Is it ethical to frighten people with a risk factor that's barely worth mentioning? Can any reasonable person justify the expense of such testing, given that it provides inactionable information?

One can envision that multiple genetic tests may be combined into one screening to increase their collective predictive power. However, there's much conflict in the scientific and medical literature on whether this is typically more effective than environmental, behavioral, and familial risk analysis (all of which are far cheaper than genetic screening).

All of these risk factors are linked together; large-scale variances in age and location influence genetic as well as behavioral and environmental risk factors. Although this fact renders it difficult to arrive at clear conclusions on the utility of genomic medicine, Hall and coworkers arrive at a number of limitations of genetic screening that suggest we should be wary of its (often) overhyped current medical benefits.

Is large-scale genetic testing cost-effective?

Large-scale genetic screening is generally not cost-effective. I can certainly understand the argument that "if it saves one life it's worth it."

We should nevertheless resist such calls. Large-scale genetic screening is only cost-effective if (1) administering preventive care to asymptomatic individuals who test positive is (2) less costly than administering preventive care to those with symptoms.

Hall and coworkers highlight the example of prostate-specific antigen to illustrate the need for skepticism in this regard. Fifteen hundred asymptomatic men need to undergo the genetic screening to prevent one death, at a cost of 80 unnecessary surgeries.

Does large-scale genetic testing modify behavior?

Knowing that you're at increased genetic risk of developing a disease later in life may cause you to change your behavior in a way to minimize the risk. Perhaps it won't change your behavior at all, negating the behavioral benefits of the test.

Hall and coworkers report that there's little evidence to support the idea that people alter their long-term behavior in response to genetic testing, e.g. in the case of breast cancer. Additionally, knowledge of genetic risk may foster fatalism in the test receipient, based on the idea that genetics trumps behavior.

On the other hand, there is evidence that genetic information leads people to buy prescription drugs, e.g. based on the idea that a drug is needed to counteract a smoking habit, although most people who smoke are able to quit without drugs. In short, genetic testing has generally not been shown to positively affect the behavior of the test recipient.

Is targeted genetic screening beneficial?

One could easily envision that targeting genetic screening to at-risk individuals may be more beneficial than large-scale genetic screening of everyone. Unfortunately, Hall and coworkers report that this idea doesn't necessarily pan out either.

Targeted screening may draw attention and/or resources away from more effective large-scale preventive care. For example, cigarette taxes and smoking restrictions have lowered smoking rates in the United States and Australia in the past few decades.

Such policies require few resources, but are clearly effective, and could likely be applied to other unhealthy lifestyle choices. In such cases, is genetic screening worth the expense and effort, and might it actually counteract other preventive efforts?

Is genetic screening susceptible to malicious misuse?

The United States recently banned genetics-based discrimination (whether this is ultimately enforceable is another question). Nevertheless, there's a history of private industry using genetics to undermine public policies aimed at minimizing use of their products.

For example, Hall and coworkers report that tobacco companies once promoted genetics as a cause of tobacco deaths, thereby partially exonerating smoking as a killer. They also report that alcohol, junk food, and gambling companies have all tried analogous strategies, with the presumed goal of minimizing public moderation efforts.

Implications.

Genetic tests can definitely be useful, e.g. in analyzing rare genetic mutations which may lead to successful drug development. Genetic testing may also be more useful on a large scale if it is combined with familial, behavioral, environmental, and observable risk factors.

However, except in isolated exceptions, genetic testing must meet a number of criteria before it is socially, financially, and ethically responsible to deploy it among the general population. Specifically, it must be cost-effective, positively modify behavior, and predict risk more effectively than cheaper methods.

As it stands today, as a general rule, genomic medicine fails on all counts. Genomic medicine should not be considered a broadly-useful medical tool until it fulfills each of the above criteria.

NOTE: The scientists' research was funded by the National Health and Medical Research Council Australia.

Hall, W. D., Mathews, R., & Morley, K. I. (2010). Being More Realistic about the Public Health Impact of Genomic Medicine PLoS Medicine, 7 (10) DOI: 10.1371/journal.pmed.1000347