Column 4 min read

Genome Culture: Redefining Health-Risk Testing

Approval of a direct-to-consumer BRCA test may be a giant step forward for 23andMe, and a giant step back for breast cancer susceptibility testing.

By Laura Hercher featured image Steven Puetzer / Getty Images

Recently, the FDA announced that consumer genetics pioneer 23andMe could begin telling customers if they test positive for one of three specific inherited mutations in the BRCA 1 and 2 genes. Mutations in either BRCA gene can cause hereditary breast and ovarian cancer syndrome (HBOC), with lifetime risks as high as 85 percent for breast cancer and 60 percent for ovarian cancer. The decision garnered considerable attention in the media, where it was alternately hailed as a great opportunity for womankind and decried as a disaster in the making, often in the same article. Both of these things are true. Let me explain.

First of all, thousands of mutations associated with HBOC have been identified in the BRCA genes. The 23andMe test reports on only three — a group of three mutations that are relatively common in the Ashkenazi Jewish population. If you are of Ashkenazi Jewish descent, the chance that you will test positive for one of these three mutations is about 1 in 40. The test is very reliable, in that it will pick up everyone with one of these three mutations. It is also accurate, in that it won’t misidentify individuals as having a mutation when they do not. So the test provides a good opportunity for anyone who gets positive results to reduce their risk as well as that of any relatives who share the mutation.

However, it’s a potentially misleading test because it looks at a tiny fraction of the possible risk-causing variants. The 23andMe test could hurt more people than it helps if the limitations of this approach aren’t clear. Testing positive is useful information but testing negative tells you very little. If someone tests negative, they should not assume that they are off the hook, especially if they have a family history of cancer. There are some very comprehensive tests for cancer susceptibility available, including some you can get online, but this is not one of them.

Public Service Announcement: If you have a family history of cancer, go see a genetic counselor.

In the clinic, the 3-mutation panel used to be offered to patients of Ashkenazi Jewish descent in lieu of more expensive testing, because it was a cost effective way to identify most of the patients in that group with a BRCA mutation. But it was always sub-optimal; up to 13 percent of Ashkenazi Jewish individuals with a BRCA mutation would be missed by this test.

Race and ethnicity are never more than mediocre proxies for genetics. Although your ethnic background may put you at higher risk for one condition, it’s not a guarantee you won’t get another. And as for that ethnic or racial identity, how sure are you? Recent studies suggest that people are frequently surprised by their own genetic genealogy. Lab rats have pure gene pools; humans do not.

As the cost of genetic testing dropped, we have moved away from ethnicity-based testing. And though it was widely covered as breaking news, what 23andMe is offering is actually a throwback. In some sense the FDA’s move here is relatively insignificant.

In other ways, however, the FDA’s decision to green light this test is a big deal — less so for what it brings us now than for what it promises to bring us down the road. Direct-to-consumer genetic testing is in a rapidly growing phase and likely represents a trend for the future, where health care will incorporate apps and at-home tests as well clinical care. And in November, the FDA vowed to make it easier for direct-to-consumer genetic testing companies to bring to market health-risk tests, with the caveat that these tests could not be diagnostic. This announcement, however, glossed over the fact that the difference between “health-risk” and “diagnostic” was often in the eye of the beholder. After all, a positive result on BRCA testing is a health-risk test for cancer, but diagnostic for HBOC syndrome, which is itself an indication for medical care.

So what this new test approval really suggests is that in the eye of the only beholder who gets to vote, the definition of health-risk test is likely to be fairly elastic, and the definition of diagnostic rather more narrowly drawn. Duly noted, FDA.