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Wednesday, 23 February 2011

My genetic counselling appointment

I started this blog to compare my experiences of taking a genetic test on the internet and having NHS genetic counselling. I have previously written about my cancer scan with deCODEme and I have outlined my family history of breast cancer which led me to request a genetic counselling appointment. I have yet to write about the counselling itself.

So here is what happened: what I learnt, whether I was offered a BRCA test and why it turns out breast cancer isn’t what I should be worrying about.

Prior to the appointment, I filled in a family tree, fleshing out the cancer cases in my relatives. The two that concerned me were on my dad’s side of the family – his sister was diagnosed with breast cancer in her 40s and his mother had a double mastectomy at age 31.

At the appointment I was given background information on the differences between hereditary cancers which tend to strike younger people and those due to the lottery of aging, which are more common after age 60. Each case of early onset cancer in my family was given a score (based on things like the age it was diagnosed, the type of cancer) and the cumulative score provided my individual risk.

Given the two cases in my family, I was assigned a lifetime risk of 17-30%. This is “moderate”, and should be compared to the average of 11%. BRCA tests on the NHS are given when the likelihood of testing positive is greater than 10%: the chance of finding such a mutation in me was estimated at 1.5% (and 7% in my aunt), so I was not offered the test.

The family tree information I had provided extended to my grandparents, but I had no information about their siblings. If it was indeed the case that my paternal grandmother was a BRCA mutation carrier and that she passed the gene to her daughter then there would be other cases of breast or ovarian cancer in her family (BRCA mutations tend not to hide their phenotypes shyly in the corner). Any new cases would increase my personal score.

I went away from the counselling session and spoke to my mum. She told me that my paternal grandmother’s parents and her siblings (a sister and brother) had all died in their 60’s, but not from cancer. My paternal grandmother had two female aunts that both lived well into their 80s.

This is not a typical BRCA mutation carrying family. I found such extra information hugely reassuring, it gives me no reason to believe that I am carrying a nasty ontological time bomb.

How do the results compare with my deCODEme DNA profiling? It is important to note that the deCODEme test did not look at BRCA itself but at other short regions of DNA that are statistically associated with breast cancer. The deCODEme result gave me a lifetime risk of 11% - significantly lower than that from my counselling and slightly below the deCODEme lifetime average of 12.5%.

It is a bit unfair to compare the internet and NHS results as they are measuring two very different things, and both in very crude ways. The NHS number was based on two occurrences of early onset breast cancer in my family, the deCODE number was a sum how associated the sequence of a handful of base pairs in my DNA are with breast cancer.

Although both came out with answers in the form of numerical values, I don’t put much value on either of the figures. The most worthwhile part of the exercise was the follow up - the lack of breast/ovarian cancer in my more distant relatives makes my odds of catching the disease seem pretty much average.

The two procedures were very different - family tree building means taking time to talk to people and hunt down information, whereas genotyping involves a click, a credit card and a consumer buzz. For those impatient, affluent and not a fan of family conversations, the computer wins hands down, but, for me, old fashioned tree building felt more meaningful. This result wasn’t as precise as a number, but it was a much more valuable in terms of personal knowledge and understanding.

There is, however, a small sting in the tail. I found my paternal grandmother’s parents and two siblings all died in their 60s. They were all killed by high blood pressure related illnesses - strokes, heart attacks - even the women. A dispassionate look at my extended family tree suggests I should not be worried about cancer, but that I should get my blood pressure checked regularly.....


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Thursday, 10 February 2011

Genetics and Pain

Last year there was a post on Body in Mind in response to an article published on the genetics of chronic pain. With refreshing honesty the author admitted he “was going to write a blog-post on it and then I read it and I was too intimidated by it.”

I had a look at the paper, with my molecular biology background, it wasn’t too scary. I was interested in the original blog post as it intersects many parts of my life. First my original training as a biochemist, second my current kiddie friendly employment as a movement teacher (which is why I follow Body in Mind) and third the long term nerve pain I have suffered since the birth of my first child.

So here is a non-geneticists run through the paper, plus some thoughts on the implications of knowing about the genetics of chronic pain.

The researchers (an international collaboration from Israel, Canada, Germany and Sweden) first studied mice. Nerves were removed from the paw of the animals in order to model the type of pain that follows nerve damage. Some mice seem to be annoyed by the numb paw which they scratch and bite. This behaviour is used as a measure of their pain.

Individual mice and mice within a strain vary in how much pain they feel, suggesting there may be a genetic component to their response. The behaviour of many mice was compared using standard genetic techniques involving inbreeding and database searches which lead to the identification of a clutch of potentially influential genes.

The researchers also looked at expression of genes in mouse paw ganglions from different strains, either from those having undergone nerve removal or a sham operation, and narrowed down the search to a gene called CACNG2. The expression of CACNG2 was turned down in mice that seemed to have more pain, and mice with mutated CACNG2 genes were shown to have different responses to nerve removal.

The corresponding gene in humans was investigated by using a group of mastectomy patients, some of whom suffered chronic pain following their operations. The researchers looked at naturally occurring differences in gene sequence in the women and found statistically significant associations between changes in two areas of the gene and chronic pain.

CACNG2 turns out to code for a protein of just the type you might expect to be involved in the control of pain response. The protein modulates AMPA receptors (ion channels gated by the neurotransmitter glutamate) by influencing their transport and probably by effecting channel gating. CACNG2 is already known to play a role in epilepsy.

The authors say their finding may be of immediate social benefit – “patients who report more pain than might be expected given the extent of their injuries are frequently stigmatised, with the suspicion that they are exaggerating their symptoms in the hope of obtaining secondary gains....knowledge of the existence of genetic factors controlling pain susceptibility....ought to reduce unwarranted stigmatization of patients with severe pain due to no fault of their own”.

I will finish with some of my thoughts on the implications of the role of genetics in chronic pain.

It doesn’t surprise me that genetics plays some part in susceptibility to long term pain, so the results in themselves do not make me feel any better about my pain. But could these findings reassure sufferers who are unaware of possible genetic vulnerabilities or even help shift the views of those who don’t believe the pain of others?

I am afraid to say that am not hopeful. Education about genetics tends to come through care providers, and I suspect only doctors who are already doing a good job communicating chronic pain knowledge would pass on new genetic findings such as these. Nothing is likely to change for patients who are currently given the impression the pain is their own fault.

Longer term, what if our DNA sequences were stored in a hospital database and we could learn of our personal genetic liabilities? Would it be helpful to know that you had a higher than average likelihood of suffering chronic pain? Or would this just create a self fulfilling prophecy?

As with genetic knowledge in other disease areas it partly depends on the type of treatment available. If stratified care for your particular genotype was offered, then you would want to know. If nothing different could be done then perhaps you wouldn’t.

And what if the genetic basis of long term pain were understood, what form would it take? It’s a fairly safe bet to say that it wouldn’t be neat and tidy. Because of the role of the sufferers’ attitudes and beliefs, their social environment and their pain escape behaviours, the genetics of chronic pain is likely to be a hodgepodge of small gene effects interwoven with environmental influences. Chronic pain also casts a wide etiological net (there are many many different causes of pain) so the underlying genetic backgrounds are likely to be similarly disparate across the population.

To my knowledge, no genome wide association studies (GWAS  - large scale systematic genetic study of hundreds or thousands of individuals) have been carried out to look at chronic pain, but many psychiatric disorders have been studied this way and the results have been disappointing. Because of the shared role of the mind in both mental illness and pain any patterns emerging from GWAS of long term pain are likely to be deeply hidden too.

I’m sure in the future we will know more about the genetic basis of chronic pain and I suspect that the inherent complexity revealed will be a little intimidating to everyone.


Nissenbaum J, Devor M, Seltzer Z, Gebauer M, Michaelis M, Tal M, Dorfman R, Abitbul-Yarkoni M, Lu Y, Elahipanah T, delCanho S, Minert A, Fried K, Persson AK, Shpigler H, Shabo E, Yakir B, Pisanté A, & Darvasi A (2010). Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2. Genome research, 20 (9), 1180-90 PMID: 20688780

For further information on genetics