Update: Nov 12th, here is the 23andMe blog on the subject
But what is behind the hype and the headlines? In this post I will look at family history and deal with EGAPP in the next.
The latest attack was sparked by a press release of some work presented at the ASHG. We don’t know too much because all we have is an abstract and a video but we have enough. FH was compared to the Navigenics genetic profile (PGS). From the abstract
“None of the 3 hereditary prostate cancer subjects were assessed as high risk on PGS. Based on FHRA, 10 subjects had hereditary breast cancer risk and PGS only identified 1 as high risk (K=0.12). None of the 9 hereditary colon cancer subjects were high risk on PGS.”
Sounds awful and this was the general message in the press, but it was not really so bad, not bad at all in fact. Why? Beacause Navigenics do not include the rare highly penetrant mutations that cause hereditary cancer, it concentrates on the common versions (no BRCA and no MMR genes), e.g. hereditary no polyposis colorectal cancer (HNPCC) makes up only about 3-5% of colorectal cancers. These are the cancers that FH picked up but which Navigenics missed, maybe because it was not looking for them?? (Maybe Navi should include them, maybe they don’t for regulatory/FDA reasons, but that’s a different issue).
What would really be much more informative would be to compare FH and genetics for the remaining 95-97% of cancers.
To be fair to Dr Eng, although I believe the study is flawed, she did say that “used in concert with family health history assessments, those tests could become more effective and accurate”
We can only really conclude that FH was better than Navigenics at finding something that FH was looking for but Navi was not. If Navi included the BRCA and MMR genes then maybe they would have at least been on the same playing field and playing the same game. (This BTW is not a correct conclusion from ABC News: Family History Better at Predicting Disease Risk Than Screening)
In any case it’s a false battle, why choose one over the other? Although proper FH is not so straightforward, it requires a lot of effort on the part of the patient, maybe weeks to contact and collect info from all the relatives – it’s not a 20 min questionnaire, there is no doubt that it is useful when available.
Family history measures genetics to a certain extent and it measures environment as well, but it’s not a full genetic analysis and of course will not detect all genetic risks, it cannot. Genetic profiles say nothing about environment. So what does this tell us? Don’t go looking for 100% concordance because you won’t find it, but while there is overlap there are also independent contributions to be made by both – they are complementary…
The Eng study was not helpful at all in comparing FH and genetics for the vast majority of the common complex diseases, it could not be with only 44 subjects. It would be interesting and useful to do a similar but much wider study on CVD or diabetes, not to see which is best but to show how and where they are complementary and how to get the best out of both.