SABCS 2012
Ethical issues associated with genomic sequencing
Dr James Evans – University of North Carolina, Chapel Hill, USA
We’re in the midst, really, of a tremendous state of change in regard to what we can do in the lab with regard to analysing tumours, analysing people and their DNA. We have now the capacity to sequence the entire genome of a person, that is all 25,000 genes, thereabouts, all the three billion nucleotides that make up your genome. This has the potential to be extraordinarily useful in clinical medicine. For example, there’s great interest in using that ability to sequence the genome of a tumour and identify what drugs an individual’s tumour might be susceptible to. My major interest is in looking at the genome of the individual who has cancer and trying to determine whether they developed that cancer because of a strong genetic predisposition. That is, has more than just academic interest because if we can determine that an individual developed cancer because of such a mutation then that gives us guidance in their treatment, it gives us tremendous guidance in how to follow them in the future, it can give us heads up for other types of cancers that they’re susceptible to that we didn’t know before and therefore they need follow-up for that. It can have incredibly important ramifications for families.
Now you’ve, I’m sure, heard of BRCA1 and BRCA2, that’s been where most of the action has been with regard to sequencing people’s DNA to figure out risk of breast cancer. But now with this new ability to sequence the entire genome we can look at many other genes, some of which are maybe not as frequently mutated as BRCA1 and 2 but nevertheless extraordinarily important for those people who carry mutations in them.
So there’s a lot of excitement about doing expanded panels and, in fact, whole genome sequencing in individuals to determine their risk of breast cancer and other cancers. There are also great problems that come up with this and I’ll just tell you one that is of interest and that is that you need to be careful what you ask when you look at somebody’s genome because your genome and my genome may carry things we don’t really want to know about. So I want to know if I’m at a very high risk for cancer that could be prevented; I don’t necessarily want to know if I am destined to get Alzheimer’s disease before the age of sixty and there are certainly people walking around with mutations in specific genes that essentially guarantee that they will get horrible unpreventable, untreatable diseases by a specific age. These are surprises that many people don’t want and certainly aren’t things that should come as surprises in the sense that if people want that information they should be really educated and counselled before getting it. So we have to figure out how to sequence people’s genes and perhaps their whole genome without also plunging us into these ethical quandaries and these difficulties. So we just need to figure out how to really harness that information and then give people what they want to know, what they’re interested in knowing but also not give them information that can not only cause a lot of anxiety but could cause them problems with getting long-term care insurance, life insurance, disability insurance and the like.
Fortunately now with the passage of the Genetic Information Non-Discrimination Act and ObamaCare we have some good protections against the misuse or the use of genetic information in that way for healthcare insurance, so we’re in very good shape there. But we have absolutely no protections when it comes to life insurance, disability insurance, long-term care insurance. So those are big questions. If you go and get your whole genome sequenced and you find out that you are going to develop a particularly delightfully named disease called fatal familial insomnia, you are going to have a lot of trouble getting long-term care insurance, life insurance, disability insurance. I have patients who have mutations in genes that strongly predispose them to serious untreatable diseases or they’re at risk of that because mum or dad had it and while they would like to know, some of them, because of things like family planning, many have foregone the opportunity to have testing because of that very point, because they’re worried about not being able to get disability insurance. One of my patients is a surgeon who knows that he has to have disability insurance so he has decided not to get such testing.
So we have this tremendous new technology, it has fantastic potential for helping us treat and prevent cancers, including breast cancer, we just have to be careful in how we apply it and we have to do so in a very thoughtful way so that we don’t get people into more trouble than they started out.
I think education of doctors and meetings like the one we’re at right now are very important because there’s a lot of information out there and I spend my life in this relatively narrow area of medicine, I don’t know anything about orthopaedic surgery, I don’t know anything about rather a lot of realms. We have to highlight the important things that people outside our field, providers outside our narrow field, need to know and that’s a good function for forums like this because that’s why I’m here, to talk about these issues to oncologists who may not have thought about these things because they’re very busy with other aspects of their practice.
I think that we have to also have standards that recommend what do you look at, what should you look at in the genome, when you’re interested in someone’s cancer predisposition. In that sense I would advocate discouraging just willy nilly whole genome sequencing because of the things I just talked about and narrowing in on the genes that we know to be important. Save the analysis of the whole genome for the research setting where you have a chance to really talk to people about what we might discover, what we might not. And then finally I think regulation plays a role. We’re seeing an up-tick in offerings by direct to consumer genetics testing companies that are offering things like whole genome sequencing. My own feeling is we do need some degree of regulation; I wouldn’t say to you, you shouldn’t be able to get the information in your genome, after all it is your genome. But I think that if you’re going to market and sell this kind of thing you should be held to certain standards and regulations will be necessary. I think those standards are that you should have to tell the truth to people because we see a lot of exaggerated claims - in many ways genomics is the snake oil of the 21st century, and number two, I would strongly advocate that there needs to be some knowledgeable professional involved in the ordering of the test and in its interpretation who is not in the employ of the company that is marketing the test. It doesn’t have to be a physician, there are many genetic counsellors out there who fit this role perfectly. They’re trained to talk to people about what’s in their genome, what they want, how to deal with that information and they have a lot of training in the medical and genetic end of it as well, so they’re technically very proficient. So I think just some common sense regulations – don’t lie to people and make sure you’ve got an unconflicted knowledgeable professional involved in it. That, I think, within those confines, it sounds great for people if they really want to explore their genome.
My message to patients would be that a) in most cases you didn’t get cancer because of your genome. Because of the hype and the excitement around genetics there’s a tendency to over-sell this message. I’m a geneticist but I would tell you that most of the reason that people get cancer is not because of their genomes. Now, if you are in that small percentage, clues can be obtained through family history; you should talk to your doctor about your family history and it might be that genetic testing is very warranted. Perhaps this very new type of sophisticated testing where we look at many, many genes could be of help to you and your family. It’s not going to be applicable to everyone but it will be a tremendous help to some people. I would just suggest that folks talk to their doctor about whether genetic analysis would be useful for them and for their family because it will be, I would say, 5-10% of people with cancer that information can be extraordinarily important. The trick is to target this new type of testing to the right people and then when you’ve found the right person to test to target which genes you really look at.
