Genetic counselling, again


I had my genetic counselling appointment today.  Although I had one previously, it was about four years ago. So the high risk program set me up for another.  I am not sure if I had a choice or not in the matter, but I certainly didn’t mind having a refresher.  The appointment was for an hour and I was able to do it over the phone, so wasn’t a big commitment.  I thought I would actually be done in half the time, but turned out we talked for the full hour.

The initial part was updating the family history.  My part-time hobby in genealogy has been helpful on this part.  But realized here that perhaps I should spend some more time on the living relatives rather than tracing the mutation back to my great-great grandfather and beyond.

Then the family update came to my mother and how she was doing.  My matter-of-fact nature that I can usually keep up to talk about these type of things broke down on that question.

After family, we got into the questions about cancer risks if I did have the mutation.  My first question is whether the risk information has been updated since we last talked.   I said this as I was staring at the 84% lifetime risk of breast cancer my mom’s Myriad report stated. And the counsellor told me that based on a 2007 study the risk is believed to actually be 40-57%.  That dumbfounded me a bit. That “80-something percent” has been in my head for four years.   Without doing anything my risk had just been halved!  Remember that previous post pondering about how to make life-altering decisions on statistics?  Besides the difficulty of weighing certain negatives (mastectomy) with the risk of an even greater negative (cancer and mastectomy), there is a whole ‘nother discussion about how to calculate the risk itself.

So this lead to a bit of discussion on the methodology of the Myriad quoted study which comes from 1998 (!!) and the more recent 2007 study.  The earlier study used 36 families and all included at least four cases of breast cancer < 60.  This is one important distinction the counsellor brought up: families were identified because they had high-penetrance of breast cancer already.  Back then BRA testing was virtually unheard by the public, so there was no means to do random or large samples.  This makes the risk numbers very susceptible to selection bias errors.  The 2007 study she mentioned to me is a meta-study.  So rather than examining families themselves, it analyzes the results of 10 risk penetrance studies.  The problem here is that the studies’ conclusions of risk are all over the map.  Here you get into statistical approaches, like DerSimonian and Laird, to try and derive a summary statistic from the studies.  Most people want to trust that people smarter than them have done the calculations right and just want a single number.  Well, the calculations are most likely correct, but the devil is in the details… like assuming the random effects which caused the studies to differ so significantly are normally distributed.

Let me try and decipher that mathspeek without butchering up the facts.  Imagine two different studies on BRCA2 mutations: one claims lifetime risk of breast cancer is 40% and the other claims 80%.  Who knows what could possibly explain the different conclusions today?  But let’s assume we could travel 50 years forward and find out it’s because different mutations have different risks.  So the true reason for the difference was that one study had far more high-risk mutation participants than the other.  A DerSimonian and Laird approach used to give an overall risk from these studies would give a number that would be completely inaccurate for an individual. (Why? Because it would be highly unlikely that all possible mutations types confer a normal-distributed risk of cancer.)

My point here is that we appear to still be thin on data and so the numbers provided by studies are highly inconsistent and questionable.  Speaking of data, that brought me to my other question: Myriad Labs has a huge repository of data given it had a virtual monopoly on BRCA tests up until last year, is it releasing its data at all?  No and not likely either, was the response I got.  This got me looking at my report again wondering why in 2009 they were still quoting a study from 1998.  But surely the reports published by Myriad today include updated studies or statistics?  Not that I have seen.  Grr, hard not to resent that company.  I am seriously tempted now to call Myriad myself and ask directly, if nothing else to let it be know that people want more open up-to-date information.  I am also even more motivated to keep watching and trying to participate in the Free My Data movement.

In the end, I did take the next step which is getting the blood requisition form.  By end of next week I hope to be sending off my blood for testing.  Hopefully, in the next 4-8 weeks I don’t stress too much.  But I am certain BRCA is going to continue to be on mind.  Will try to translate my worries to more productive purposes like blog posts on latest research findings for BRCA and emerging public databases.


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