A Test You Shouldn't Jump At

By H. Gilbert Welch
Special to The Washington Post
Tuesday, February 19, 2008

In the effort to find a better way to identify which men will develop prostate cancer, the second most common cause of cancer death in men, the New England Journal of Medicine seems poised to announce a breakthrough. Later this month, the journal will publish a study showing how a combination of five gene variants -- so-called single nucleotide polymorphisms -- can help predict a man's risk of getting the disease. In the press release for the study, which has already been posted online, the authors wrote, "For the first time, this type of study has made it possible to develop a clinically viable gene test."

Genetic testing is a competitive area of research (the authors themselves are forming a company to market their test). But those of us who are potential consumers need to have a little healthy skepticism about the claim of clinical viability.

What does "viable" mean? It could mean that the test is able to be done. Or it could mean it's worth doing. If you are interested in the latter, here are three questions you'll want to ask:

What can the test tell you about your risk?

The study tested men with and without prostate cancer for 16 genetic variants. Although all 16 had been previously associated with prostate cancer by other researchers, this study showed that three variants had no relationship with the disease. This highlights an important caveat about genetic information: We now have the ability to read so many variants that some will appear to be related to a disease simply by chance. Before you believe a purported gene-disease association, you'll want to see it replicated in multiple studies.

The researchers went on to choose the five variants most strongly related to prostate cancer.

Even these five variants were, in the authors' own words, "only moderately associated with prostate cancer." Thus, they examined the cumulative effect of having multiple variants. The result was an apparently powerful association: Men who carry four (or all five) variants have 4.5 times the risk of developing prostate cancer compared with men who have none.

But it's rare for a man to have none of the five variants -- only 10 percent of men without prostate cancer had zero variants. The base case should reflect the typical man, and the typical man has two variants.

The base case used to calculate the change in risk matters a lot. Using zero gene variants as the base suggests that a man with any other test result is at an elevated risk. But, in fact, a man with two variants is at average risk.

And no one has their risk increased 4.5 fold. Instead, the biggest change is either a doubling of risk or a halving of risk.

Risk of what?

Getting prostate cancer isn't the same thing as dying from it. Prostate cancer is the poster child for an increasingly recognized side effect of early cancer detection: overdiagnosis, or the detection of cancers that will never matter to patients.

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