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If you’ve been following health issues for the last decade or so, you must have noticed that genes are all the rage. Hardly a day goes by that doesn’t carry news of some breakthrough about a gene that is claimed to explain one disease or personality characteristic or another.
In preparation for writing this post, I did a google search for “gene explains heavy breathing,“ and I found a story. Try it yourself: pick some condition or characteristic that strikes you as in the range of normal, and see if a gene has been found to help explain it. Tell me if you don’t find something.
And keep in mind as you read this post that, if genes are really destiny, then it’s a good thing I didn’t have kids, given my health history.
The Breast Cancer Context
In the realm of diseases, there is an enormous focus on the genetic “causes” of illness. In breast cancer, 2 genes have been identified as linked to inherited susceptibility to the disease. These genes are cleverly called BR(breast)CA(cancer)1 and 2.
If you have a strong family history of breast and/or ovarian cancer – defined as at least two first degree relatives, especially if they were pre-menopausal at diagnosis — the odds are you carry an inherited mutation on one of these two genes. And if you carry one of these mutations, your risk of getting the disease goes up, sometimes way up.
Notice I didn’t say that the odds are you carry one of the two genes. We humans all have all the same genes. It’s the mutations – the changes in the structure of the genes – that either we inherit or that occur from a lifetime of different exposures to various things – that increase the risk of disease.
Notice, too, that I didn’t say that, even if you have one these mutations you will get the disease. I said your risk increases. I did not say “will get breast cancer,” because even in cases where the risk from the mutation is very high, 15 to 25% of people who inherited the mutation do not get the disease.
So, genes alone are not causing breast cancer, or anything else. Something has to happen to the genes to make them go haywire and trigger disease. And whether your body will respond to whatever that trigger is, no one can say for sure.
Two other things about the “breast cancer genes.”
1) BRCA 1 and 2 are patented by Myriad Genetics. They’re not the only human genes that are patented, but they are the most famous. Gene patents inhibit research and limit the amount of the information available to patients. The breast cancer gene patents are being challenged in a ground-breaking lawsuit led by the ACLU and the Public Patent Foundation. Breast Cancer Action was the first – and, for a long time, the only – breast cancer organization to sign on as a plaintiff in this lawsuit.
2) When BRCA1 and 2 were found, researchers were sure they would find BRCA3 and 4 very quickly thereafter. The researchers were wrong, and the hunt has pretty much been abandoned.
Genetic Testing: An Art More Than A Science
As more and more disease-related genes have been found, tests have become available to identify these genes in people. Gene tests are done from blood taken from a simple blood draw.
But reporting the results to patients is not so simple. The issues can be very complicated. What do the results mean for whether the patients will become ill? What do they tell her/him about how to lead life despite or with the results? What do the results mean for the immediate family of the patient, especially brothers and sisters who come from the same genetic background? The discussions are long and involved.
Fortunately, a professional field of trained genetics counselors has emerged. These folks are trained not only in genetics, but in how to talk to people about gene test results. At Breast Cancer Action, we always encouraged people who were considering genetic testing to consult a trained genetics counselor.
Working with trained genetics counselors is better for patients, and for the health care providers who otherwise find themselves in the uncomfortable position having to explain things they may not be equipped to explain.
The ALS Context
Because I had an older sister, Ruth, who died of ALS, neurologists think there has to be some inherited genetic component to my illness. While I always resisted being tested for the breast cancer gene mutations, I decided to be tested in the ALS context. One reason is that the results might help researchers understand more about a disease about which very little is known. The other reason is that I have nieces and nephews of child-bearing age who might want to consider the risk, if I have a mutation, that they might have it, too, and consider that risk as they think about having kids.
But ALS is not breast cancer. First of all, the disease is rare – certainly compared to breast cancer — striking 5600 Americans each year. (For comparison, approximately 260,000
U.S. women are told each year that they have breast cancer.) Of that number, 5% of ALS cases are considered “familial,” with multiple members of the same family having the disease. It’s this 5%– 280 people a year — that is the focus of the genetic research in ALS.
And genetic mutations have indeed been found: SOD1 is the most common and has been the most studied. It is believed to be responsible for as little as 10% and as much as 25% of familial ALS, though how it triggers the disease is not understood. That range (10% to 25%) is a very good indication of how little is known about the genetics of familial ALS.
Other gene mutations associated with familial onset have also been identified. They are
rarer than SOD1 and their “penetrance” (the proportion of people with the mutation who go on to get ALS) is lower than for SOD1.
All of these mutations can be tested for, but together they explain only about 30% of all cases of familial ALS. Which means that 70% of familial cases are unexplained. In other words, a negative gene test in a person whose family has more than one case of ALS is more likely than not to get a negative gene test result. Which is what happened in my case.
Learning Gene Test Results: The Good and the Bad
I learned my test results from a very nice and caring person, a trained nurse and clinical research specialist at the Forbes Norris Center where I’m being seen for ALS. I was a little surprised to learn the results when I did, because I was at the Center for a follow- up visit related to a clinical trial in which I’m participating. Gene test results were not, as far as I knew, on the agenda for that day. And there wasn’t a trained genetics counselor in sight.
The conversation started when the nurse said to me something like, “I don’t recall whether you are someone who wanted to know the gene tests results or not.” That seemed more than a little odd to me, since that information should be in my medical chart, somewhere near the consent form I signed for the genetic test.
When I indicated that I did want to know the results – in order to be helpful to the rest of my family – the nurse said that my results came back classified as “unknown,” meaning that none of the identified genes had been found.
The nurse said that none of the genes had been found. I never heard the word mutation mentioned, though the difference between genes and mutations is a very important distinction. I’m sure the genes were found – we all have them, after all – but that none of the known mutations associated with ALS was found.
What bothered me as much was the discussion about how likely it was that I had a familial form of ALS, despite the results of my gene test. The nurse pretty much insisted that, if I had a sister who had had ALS, there had to be a familial genetic component. This was especially true, from her perspective, because so much of familial ALS cannot be explained by the gene tests that can be done at this time. Of course, if your perspective is genetics, this makes sense because the thinking is “It must be genes, we just haven’t found the right ones yet.”
If your perspective isn’t genetics, the thing to say might be as simple – and as shocking in the medical field – as “We don’t know.”
The limited view held by the nurse fails to take into account how little genes can tell us about our health. My sister and I grew up in the same family, in the same house, exposed to the same things in our common environment at an early age. But it seems no one is looking to see whether those common exposures might explain either her disease or mine.
No one is helped when medical professionals insist we know what we don’t. Thinking outside the box will never happen if we can’t see that we’re in a box to begin with. If we look only for genes, that’s all we’ll find. If we open our minds to other possibilities, we just might find other explanations.
© Barbara A. Brenner 2011
Thank you for that fabulous article. Your perspective on medicine and medical care are invaluable.
Your clarity, and willingness to share and explore, are breathtaking. I praise you for telling everyone who sees this blog just where you are TODAY. There are, of course, histories – biological, familial, social, medical, and many more – but you have woven such a good tale of the here and now, and have illuminated why many people aren’t encouraged to “think outside the box” – we all need collaborators on our journeys, and it is hard to find a place to say “what if…”. May you continue searching, and bringing your fine brain to all of the new work you are doing !! Fondly, Mary
P.S. Haven’t yet figured out if there is a “chat” aspect to your blog; please advise.
I didn’t know BCA had joined the suit against patenting of genetic material. I find patenting of naturally occurring substances appalling and totally contrary to the concept of “invention”.
It’s always comforting to have “answers” or neat explanations. Your genetic test results demonstrate once again how limited our knowledge is. No matter how unsatisfying and frustrating the results, as with so many things in life, the answer is that’s just the way it is.
I have messed up genes, I have BRCA 2. It tried to kill me. Twice. And, sadly, I reproduced. When you say that “15% of genetic screw up won’t get breast cancer” that means 85% will. And what fun that is! And then you will probably (80% or so) get Ovarian Cancer…at Stage 4 which is when they can find it – and you will have a 9 in 10 chance of dying from it. Within 2 years. Oh, there is a 20% (maybe) chance that your ovaries won’t just explode and kill you…want to take those odds?
Tell me again that genes are not destiny !
OK: I am not fond of Medical Dominance….I know they are not Gods, and find that many in that profession don’t know that. And I am as smart, if not smarter, than the folks who treated me. But, I also took a drug that gave me a 3-5% survival advantage. That’s a whopping 86% chance of it doing nothing but giving me side effects. Whoppie. But I wanted that 3-5%.
We know environmental factors play a part, we know that lots of co-factors exist. But we don’t have medical records on the population. We don’t track citizens, and we don’t have information on the thousands who grew up in LA smog, and moved to clean air towns whose water table is poisoned by overflowing cattle waste ponds. We know Things are Related, and messed up.
But someone is willing to put money into genetics. It may not be the best choice of where to plop medical research money: but it’s there. And Things are learned. My taxes paid for the research and I want the results. And I think any information is good. Any genetic mutations they can find are helpful. And hold hope for finding out more information. Maybe like the “K-ras” mutation that gives info on weather drug B will “work” for a patient or not. It’s not clinically useful for the treatment of colo-rectal cancer…but it is useful for research into drug therapy tailored so that someday everyone is not just given a chemo drug that may not help them at all.
Don’t throw the Baby Out with The Bath Water. Genetics are a big deal. Not the only big deal, but a big one. And if I had had the information that my genes contained a time bomb that would end life-as-I-knew-it…. I would have done something about it. Gene studies will allow my descendents to have a different fate.
Information is power to make choices. And when you must make choices, any real information is better than none.
Myriad Genetics (the monopoly test provider mentioned in your excellent blog) publishes a “patient’s guide to risk assessment” that genetic counselors hand out to clients when they come in for advice about the test for the breast cancer mutations. A pie chart that tries to identify the sources of the disease identifies about 8-10% of all breast cancers as “hereditary” but estimates that about three times as many diagnoses belong to a category it calls “familial,” that is, occurring among women in families where other relatives have also been diagnosed with the disease but where, like you and the ALS genetic test, they turn out NOT to be carriers of any of the known mutations. The pamphlet offers no explanation for this ambiguous finding, no suggestion of any shared environmental histories and certainly no mention of the possibility of other (yet to be identified) genetic mutations that might or might not play a significant role in causing this disease. I presume that Myriad’s estimate that 30% of diagnoses can be attributed to “familial” cancers derives from their own test results. These cancers should clearly be the target of research. But who is paying attention to them?
Incisive and provocative as always!
Every time I read one of your blogs I feel that I am receiving a much overdue science lesson. Thank you for increasing my knowledge base. Your choice of images that supplement your blogs are simultaneously complementary and ironic.
Thanks for this, Barbara. I appreciate how you are using your current condition to make general observations about breast cancer and medical situations generally. You are clear and helpful. Always look for alternative explanations (in your account, you note that you and Ruth, growing up in the same household, were exposed to similar things. I recall when first reading up on ALS last fall that there was an unusually high incidence of ALS among Italian footballers (soccer players), indicating possible exposure to toxis substances such as pesticides used on playing field grass.
It amazes me to no end how insightful you are to these medical issues and that in more than many cases you are more insightful than the medical professionals! While this is a true testament to you, it should be a bit embarrassing to people who are supposed to be educated…especially in these specific fields. Much love (as always) and keep writing!!!
The more of your comments I read, the more confused I become. How nice when answers are straightforward and have no subtleties. Maybe that explains the approach most TV news and even newspaper articles follow.
Perhaps family history or genetics are flawed in explaining why we develop diseases or disorders, and perhaps problems that run in families can be attributed to environmental factors to which the members of that family have been exposed, rather than a shared heredity. Certainly these possibilities need to be considered by people contemplating drastic steps (not having children, having breasts and ovaries removed) based on genetic testing results.
I wonder whether it would be helpful for scientific research if all the people who have developed breast cancer are tested for the known genes, since that number seems large enough that if a significant amount have the gene mutation it can be determined that the mutation is the ultimate cause of the disease. It still wouldn’t explain what causes the mutation, although it might make it easier to see if and what environmental factors are the trigger. But if only a small number of the people with breast cancer have the mutation, that information would be helpful in focusing research more on environmental and other causes.
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