Angelina Jolie tested for one gene, what about the other 20,000?

Angelina Jolie finds out she has a genetic predisposition to breast and ovarian cancer
Angelina Jolie acts on genetic testing results

The world reacted with shock as Angelina Jolie, Hollywood actress, UN Ambassador and world renowned beauty announced in the New York Times that she had undergone a ‘cancer risk reducing’ mastectomy to decrease her chances of developing breast cancer. She had previously had genetic testing that had revealed she was a BRCA1 (Breast Cancer Gene 1) gene fault carrier and thus has a significantly increased risk of developing both breast and ovarian cancer. The testing was initiated because her own mother had died of ovarian cancer (ovarian and breast cancer are both linked to the BRCA1 gene). The most effective way to reduce this risk is to remove the tissues that can become cancerous, i.e. the breasts and ovaries.

Angelina had a genetic test for a single gene, she was alerted to this because of her family history of cancer. However, she could have also found the same information if she had had a ‘full genome sequence’ done where all of her 20,000 genes (including the BRCA1 gene) could have been analysed.  This kind of generic testing is technically possible and is beginning to appear in health services across the world.  In fact, in the UK next year, the 100,000 genomes project will arrive in the NHS – where 100,000 people will have their genome (i.e. all 20,000+ genes) analysed to explore their genetic predispositions to disease. The practicalities of this service are still being worked out: for example how will this testing be offered? To whom? And what information will be shared? Although it is likely that 20,000 genes will be explored for each individual, it is very unlikely that all 20,000 results will be fed back to that individual. This is because the vast majority of these results will have uncertain or unknown impact and will also be totally unrelated to the clinical question the doctors want to answer.  However, amongst these 20,000 genes there may well be some that patients would be particularly interested in knowing more about.

A very topical debate for those of us working in this area relates to how to interpret genetic results, e.g. relating to the BRCA1 gene, for people who have no family history of cancer (and who have lots of unaffected female relatives).  Genes don’t work in isolation, they are affected by their environment which could include the external environment (e.g. smoking, diet, exercise etc) or the internal environment (e.g. other genes).  So, if a BRCA1 gene fault is identified for someone who has no family history of breast or ovarian cancer, it is difficult to know if this is likely to cause this cancer or not.  BRCA1 gene faults are however particularly virulent in certain very specific populations, for example, in the Ashkenazi Jewish population.  With this group, having a BRCA1 gene fault, even in the absence of a family history, is likely to be predictive of cancer.

There is very little population data on the clinical significance of many supposedly deadly genes, i.e. there are likely to be people out there with BRCA1 gene faults who won’t ever get cancer and we don’t yet know what is protecting them (is it the presence of another gene, is it something they are doing in their lifestyle?)  It is this difficulty with interpretation that is at the heart of discussion within the genetics field at the moment. Patients themselves say very clearly that they want access to information, even though it may be uncertain or difficult to interpret. They want to be able to make decisions about their own health, just as Angelina has done. However, in the absence of a family history – the one clear piece of evidence that shows how the genes are playing out – it is so difficult to know for many genes as to whether they will cause mayhem or not.  Having breast and ovaries removed is a major, life changing decision, one that cannot be embarked upon lightly. It is not the same as a cosmetic breast augmentation and for many the aesthetic result is difficult to reconcile. However, to prevent cancer and potentially save a life, this is a price worth paying, particularly for women who have seen their female relatives die at a young age.

Having all 20,000 genes explored via a genome sequence sounds great – a full genetic MOT; but what to do with the results; how to interpret them; and what actions to take are all questions that are still being worked out. What Angelina has done in terms of testing, empowerment and action is logical. Unfortunately for many, the path to take following genetic testing results, particularly when a whole genome is analysed, may be much less clear-cut.

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