New Prostate Cancer Tests
Spetember 12, 2013
Dr. Daniel Lieber
Dr. Steve Hershman
D. Mitteldorf Hello and welcome. This is Darryl Mitteldorf. I’m Executive Director of Malecare Cancer Support, the organization that was founded in 1997 and has grown to be our nation’s largest men’s cancer support and survivor national nonprofit organization. Tonight is our September 2013 teleconference, another in our monthly series of teleconferences on information by and for prostate cancer survivors, and tonight will be about genomics and the new world of testing that’s available to prostate cancer survivors.
We have 887 people listening in. Welcome to you all. There’ll probably be many, many more of you listening to the online archive of this broadcast, as well as reading the transcript. Welcome to you.
Tonight we’re joined by Dr. Daniel Lieber and Dr. Steve Hershman. Both Dr. Lieber and Dr. Hershman are PhD graduates of Harvard University System Biology program, which they’ll describe more about their studies. Between the two of them, they have about a decade of experience analyzing genomic data and have expressed personal and professional interest in working with our prostate cancer survivor community.
Tonight’s teleconference will be moderated by Joel Nowak, who many of you have heard before on previous teleconferences. Joel is a social worker and Director of Malecare’s Advanced Stage Disease program and also our Advocacy program.
Gentlemen, the show is yours.
J. Nowak Thank you so much, Darryl. I’d like to welcome everybody, and also I join Darryl in saying how excited I am that we have both Dr. Lieber and Dr. Hershman with us tonight. Just very simply I want to just jump into the topic.
The first thing I would like to talk about is that we certainly hear a lot about genetics and its role in cancer in the media. I would actually like it if you could please share with us what is genetics and the genome and why is it important to cancer survivors?
Dr. Lieber Sure thing. First of all this is Dr. Daniel Lieber. Thanks so much for having us on. It’s our pleasure and our privilege to be able to … topic and we look forward to a great dialog in the coming minutes and as well as beyond that.
I guess the question was what is genetics and why is it important to our understanding in cancer. Before really diving into that topic, I think it’s worthwhile to give a solid background on genetics to bring everyone up to speed and make sure that everyone is on the same page.
What is genetics? Genetics is the study of genes and heredity. Specifically it’s focused on how we differ, we humans amongst individuals, and the impact that that has on our ancestry and on our health. One of the key dogmas of molecular biology is that DNA is the foundation upon which everything is built and the DNA is turned into RNA, which is turned into protein. DNA is similar to a book that’s read by every one of our cells. RNA is similar to the blueprint that codes for the products that will be produced. And proteins are the actual products, the actual marker and machines that are in the cell and actually do the work to make our bodies work.
Our DNA is organized into genes. Genes are simply strings of DNA and many genes are packed into a single chromosome that each of us has 23 different chromosomes in every one of our cells and actually in duplicate because of course we inherit one copy from each of our parents. The genome is three billion bases long. It’s formed of letters, essentially, which can be either A, G, C or T. The book of our genomes is actually three billion bases long, which is a huge wealth of information.
Interestingly, we all differ at around three million sites throughout our genome. That’s the same as if you were reading a book, one in every thousand letters there’s a difference or a mistake between every one of our genomes. These mutations are not always bad, nor are they always good. Some of these mutations are actually quite common, and these we actually tend to call variance rather than mutations, and they’re mostly benign and really don’t have a huge impact on function. While some others of these mutations are actually quite rare, and these rare mutations can either also be benign or they can sometimes be harmful and lead to disease.
As to why is genetics important for understanding disease, there are a number of ways in which it’s important. First of all, as we all know, rare genetic mutations can lead to a predisposition to cancer and other diseases. Some of the more famous examples is a gene called BRCA1, which many of us have heard of, but what’s very interesting is that there’s a phenomenon called acute hit model for cancer, where each of us has two copies of DNA in our cells.
If we are born with one of these copies altered, then there’s a much higher chance that in some of our cells if a mistake occurs when the DNA is replicating, then the second copy of that gene will actually be knocked out and, therefore, we’ll have two dysfunctional copies of that gene. That’s exactly how BRCA1 with breast cancer and also sometimes with prostate cancer works through that model.
That’s speaking about these rare mutations in our genome, but, as I said, there are also very common mutations in our genome. What’s interesting is that these common genetic mutations can have small increases or decreases of risk, of disease risk. There are actually studies to try and identify common genetic variance that are associated with various diseases, including prostate cancer. These studies are often called genome-wide association studies, or GWA studies. These can have a powerful impact on identifying the gene that takes part in pathogenesis. What’s amazing is that these findings can actually lead to pharmaceutical companies developing drugs targeting those genes.
Finally, I’ll say that genetics also plays a role in which drugs you should take, both in terms of how efficacious a drug is, as well as whether a drug is safe or not for you to take. I’ll stop there.
J. Nowak If I could try to put it in perspective that the genes are what signal the eventual development of the proteins, and by looking for mistakes in these genes we can through a correlation, I assume that that’s correct, make some assumptions, some predictive assumptions. For instance, if we know that there’s an error at a particular gene, that that may make someone more susceptible to develop a cancer, in this case prostate cancer. Would that be correct?
M That would be absolutely correct. Genetics is a way getting under the hood of biology and beginning to see how things work. To give you an example of what you just described there is a gene that’s involved in the development of organisms. It patterns things throughout your body. It’s called HOXB13. There’s a mutation that’s found in this gene not too commonly, but in a number of people, where it’ll increase your prostate cancer risk by about 10 to 20 fold. … does, it actually interacts with some other genes that are involved with testosterone sensing, the antigen receptor, and this is a pathway that’s well implicated in disease. By finding examples like these, we begin to see at a deeper level all the different biological causes for cancer to come about, and we can then make better connections between them and then make better strategies as to how you can begin to treat cancer and its root causes.
J. Nowak Right. If I were to go in—now I know you’re not physicians, so if this is something you’re not comfortable answering, but if I were to go in and have a genetic study done and we find that I have a gene that says that I am susceptible or at higher risk, what would my next steps be?
M That’s the million dollar question. Information is all good and all. Information is power, but that’s not actually true. It’s information plus action that’s power. If you learn that you’re at higher risk for a disease, typically there are interventions out there, but we don’t yet know that much about what you can do.
In the example of prostate cancer, if you learn that you’re at a higher risk, I want to give a disclaimer here that there are a number of reasons why you can be a high risk because of genetics, but also a number of reasons why you be at high risk not because of genetics; or you could be at low risk because of either. If you believe your risk is high, you could do things, such as having more frequent exams.
There are also some drugs and there are clinical trials that have been done with them about things that could help prevent prostate cancer. There is a classic compound called 5-alpha-reductase inhibitors. One of these is finasteride. There was a study that showed that it was able to reduce prostate cancer by about a third, with a caveat that some people have actually increased the occurrence of late stage aggressive tumors.
It’s still early days in figuring out interventions if you know you’re at high risk, but there are definitely practical things you can do.
J. Nowak Right. Obviously if you know you’re at risk, you need to create a surveillance program and perhaps consider adding one of the 5 AR inhibitors after consulting with your physician. Now we also know that there seems to be a familial link with certain cancers including prostate cancer. Can one assume that that’s related to the genetics, perhaps mutations that we’re born with that have been passed on through our family?
M You can. I’ve seen various numbers that describe the percent of prostate cancer cases that can be attributed to familial history. I’ve seen one figure that it was about 20% of cases, and of cases that were linked to familial history where there is one rare variant that has a high impact; that’s probably more like 5% of the cases of prostate cancer.
J. Nowak And would these—I’m sorry; go ahead.
M I should say that while there are genetic factors that explain the familial links for prostate cancer, there’s a lot of redundant information between genetic tests and family history. In that if you know you have ancestors with prostate cancer, even if you get a genetic test that comes back negative, you still may be at a higher risk because there are other genetic factors that might have been measured by that test.
J. Nowak Right, but if you do find that you are at higher risk, I assume that this would be specifically for first degree relatives. How far out would that risk be expected to be seen? Is there any way of knowing?
M It can go further out. There is a way of knowing if you measure your DNA in various says, but as a rule of thumb as you go out from like a first cousin to a second to a close relative to a further relative, you would want to sort of see multiple number of those relatives with the condition to have the same influence. The way genetics works is about half of your genetics comes from each of your parents.
The flip side of that is you only have half of your parents’ DNA. If you go back, your parents’ life after your grandparents’ DNA, but by looking at your family tree, you can see how related you are to various members of your family and how much of your DNA that you would share with them.
J. Nowak Right, has there been any research? We often see that prostate cancer goes along with a family history if you look back to other hormonally regulated cancers, breast cancer. I don’t know whether bladder cancer is considered hormonally, but certainly you can see a lot of men with both cancers. Is that a genetic link that’s in there, or is that just a coincidence?
M Yes, there have been lots of studies of familial history and how that affects risk of cancer within prostate cancer. Having one first degree relative increases your risk of prostate cancer by 2.5 fold. That actually having a brother with prostate cancer increases your risk more than having a father with prostate cancer.
There’s also a difference between the age at which prostate cancer is developed and the genetic risk. Having an affected relative who got prostate cancer at a very young age actually increases your risk more than if that relative had prostate cancer at an older age.
What’s also interesting is there is some overlap between different forms of cancer so, for example, because some of the underlying genetic factors are actually shared, so one example is that some studies have shown that individuals with a family history of breast cancer actually have a slightly increased risk of prostate cancer. The thinking is that there are some genes, for example, BRCA1 and 2, which certainly play a role in both breast cancer and in prostate cancer and that may partially explain the increased risk there.
J. Nowak We’re talking generally, and general population wise, but we know that within our prostate cancer community there’s some extraordinary disparity in incidence and mortality between African Americans presenting with prostate cancer and Caucasian Americans presenting with prostate cancer. When we talk about genetics and risk, should we keep the idea in the back of our head that perhaps risk is perhaps even as much as doubled around genetic determination for African Americans; or is racial disparity already taken into account when we talk about incidence rates using genetic descriptions?
M My understanding is that they’re actually independent. It’s known that African Americans have greatly increased risks of prostate cancer and of actually of dying from prostate cancer compared to Caucasians. I believe Asians actually have the lowest risk of prostate cancer.
Interesting, most of the studies to date have mostly been in Caucasian and the genes identified, especially the common genetic mutation, have been identified in Caucasians and then once they’re identified in that population, they then get tested in other populations. This is starting to change as different research groups are gaining tens of thousands of individuals from other ethnicities; but we’re still at a relatively early stage of figuring out the genetic basis of every ethnicity, so it’s still early days.
M If I could jump in and just answer that, while there are different risk levels of prostate cancer based on ethnicity, it’s important to point out that there’s also a lot of variability within an ethnicity for your risk of prostate cancer. People who are at the highest genetic risk of prostate cancer can have a five fold higher risk than the average person. That’s much more than the risk between ethnicities.
J. Nowak We certainly have the genetic root in our risk, but I know that one of the big issues that many men have when they’re initially diagnosed with prostate cancer is the aggressiveness that that cancer as they try to make decisions for treatment. This actually extends for men who have had a reoccurrence if they’re trying to decide on how aggressive of treatment to take. Is there any root place that genetics can direct us as to understanding the nature or the aggressiveness of our cancer and being able to make treatment decisions for there?
M Absolutely, and there are a number of ways that it can be done. If you want to note the aggressiveness of a cancer I want to begin by saying it’s important to do a measurement based on the cancer itself. You don’t want to take an average healthy tissue and do a measurement off that. If you give a saliva sample and do a genetic test based on that, it probably won’t tell you what’s happening in your prostate all that well. What you can do is if there was a biopsy that was taken from the prostate cancer, you can then do DNA sequencing of that cancer, and you can begin to see what mutations occurred in the cancer that made it what it is. Using that information, you can predict how likely it is to advance to the next stage. You may also be able to figure out which drug may be efficacious to treat it.
This is sort of cutting edge science and I don’t know how commonly it’s happening clinically, but they’re now beginning to be actually a cottage industry of providers, who will take prostate cancer tumors and do DNA sequencing. In addition to DNA measures, there’s also a whole host of various biomarkers. I’m going to cluster together measurements of RNA, of protein, even of metabolites. These are things that can be measured by taking a sample from somebody’s body. It can vary from a tumor or even to urine or even a blood test. These are another way you can get at the biological state of the cancer. To put this another way, you do a DNA measure and actually see what the instruction set is, but you also see what programs are running within the cancer by measuring from these biomarkers.
J. Nowak Right. Actually there are two tests that are starting to be used and I think that actually do that. That’s the Oncotype DX prostate and Prolaris. Are you familiar with those tests?
M We’re a little bit familiar with them.
J. Nowak I assume and I believe that these actually measure the tumor itself, either through biopsy or closed surgery, and look for these markers.
M My understanding is that they’re taken from a tumor biopsy. In these tests they’re not sequencing the DNA; instead they’re sequencing the RNA. They want to know which genes are turned on and which genes are turned off. My understanding of how these tests work is the companies that developed them have databases of probably thousands of cancers, some that are aggressive and some which were not aggressive, and in these cancers they probably measured tens of thousands of different genes seeing how highly expressed they were. What they’ve done is they’ve found patterns. That’s the genes where people get their expression signature; they’re able to predict whether it’s going to be an aggressive cancer or a not so aggressive cancer.
On a commercial scale what they’re doing is they’ll take a tumor biopsy and they’ll then sequence a subset of the genes in it, and from the expression level of the subset of the genes, they’ll then give a prediction score as to how likely the cancer will be aggressive.
J. Nowak That’s to predict, that’s predicting or we’re looking at a statistical prediction. It’s not that it is aggressive or not. Is that correct?
M Yes, that’s correct.
J. Nowak I guess that one would really need to take the other information we have, the PSA, a Gleason score on the biopsy, and use that information along with the results of these genetic or RNA tests in order to make a more informed decision.
M Absolutely. The challenge in the field is trying to figure out how to integrate all of these data streams, because they all inform each other, but it’s going to take a little while for medicine to learn how to best integrate everything and to provide good guideline.
J. Nowak Right. I think that that’s an excellent analysis. You also mentioned that the DNA or the genetics can also inform treatment decisions. We’ve talked about prediction. We’ve talked a little bit about deciding what treatments to take based on aggressiveness, but I think also within the area of personalized medicine we’re moving into an area where we can help inform some of our treatment decisions. Could you talk a little bit about that?
M Sure. There are a number of companies that are essentially trying to build up databases of what to do, what treatments to give given certain biomarkers or DNA markers that are found in your tumor. One example of a company in that space is called Foundation Medicine, which looks at a number of different types of tumors. What they do is they sequence 100 genes that are known to cause various forms of cancer. Many of these genes actually have drugs that have been developed to specifically target these genes.
What they’re able to do in some but not all cases, it is to identify mutations within a cancer and then essentially connect that with a drug that may have been prescribed for a different kind of cancer. The hypothesis is that perhaps that drug may or may not have been used and may actually be helpful for treating a different form of cancer than it was normally indicated for.
J. Nowak Would it be correct to assume that for the most part that when a pharmaceutical has an approved drug that they would not be as interested in developing a genetic test that could evaluate whether it’s the right drug because the economic value even of seeing their drug being used when it doesn’t work for three, four, or five months may actually be at play?
M It’s actually really complicated. The FDA currently is putting a lot of pressure on pharmaceutical companies to try to have them be more targeted. There’s a thing that they used called companion diagnostics, which is the idea that in addition to trying to apply to get a drug through the FDA, you also have diagnostic tests to send through with it that will help predict whether or not the drug is effective.
While it’s true that if a drug isn’t effective on some people and they don’t the get people, the pharmaceutical company will make less money, there are some reasons for them to try to buy into this whole personal diagnostic vision. If you know that drug is more effective, you’re then able to run smaller, leaner clinical trials, and they’re more likely to be successful. When they’re successful, if the drug is effective in a higher percentage of individuals, that might make doctors more likely to prescribe the drug or insurance companies more willing to pay for it.
J. Nowak Are there any situations that you could share with us where you know that the pharmaceutical companies have actually develop that and it’s in use?
Dr. Hershman Yes, the one that I think is the most exciting to happen recently is the drug not all related to prostate cancer, but related to cystic fibrosis. It’s called Kalydeco and it was developed by Vertex Pharmaceuticals with the cystic fibrosis community.
What’s interesting about it is they developed it by targeting a patient population that only makes up about 5% of all patients with cystic fibrosis. There are well under 10,000 people with this mutation in the United States.
Yet by making a very targeted drug, the company was able to run very lean clinical trials. They were able to work with the patient community in order to develop them. They were able to get a nice reimbursement for the drug. I believe it’s hundreds of thousands of dollars per year. They’re actually impacting patient’s lives in a very small time span. I believe this drug was able to skip phase III clinical trials because it was so effective.
In prostrate cancer there are actually some good examples of cases where it’s been discovered that there’s a recurrent mutation seen in many people’s prostate cancer, and there are people who have now begun to develop drugs for it.
Danny, I think I should hand it over to you to talk a little bit more about this.
Dr. Lieber Steve, that’s a really good point. One of the most common genetic alterations found in prostate cancer is a fusion of two genes, one called TMPRSS2 and the other is called ERG4UPX. This is actually a gene fusion, so two different genes that were placed out of their original locations and fused together. It was actually found in around half of cases of prostate cancer and is supposedly a very early molecular event in the development of the tumor.
Various labs and in collaboration with some pharmaceutical companies are trying to use certain drugs, there’s one class of drugs called PARP inhibitors, and then other molecules as well in order to try and specifically target this molecule in order to create and improve targeted therapies. In addition, there are also clinical trials that are currently ongoing where they take existing drugs for prostate cancer and then try and segregate the population into two bands essentially, those with and without this genetic alteration, in order to see whether or not this genetic alteration is associated with an improved outcome of drugs that are already existing. These are some ways in which … markers are improving the efficiency of drug ….
J. Nowak Okay. Looking forward, the use of genetics, our understanding of genetics is relatively new, where do you see the future for genetics and cancer?
M We see the future at all stages of the process. We think that there’s a progress to treating cancer and at all stages genetics might be able to play a role. The first stage is knowing how often you want to screen for that, what is your background of genetic risk and we discussed some environmental factors about this, but also genetic factors. There have been some recent studies that have brought the number of regions of the genome that are associated with prostate cancer up to over 77. Now we’re now able to explain roughly a third of all the genetic causes of prostate cancer.
In this information there could come a day where when you go to a doctor they’ll have a background idea in the back of their mind how much of a genetic risk you have. They’ll then ask you about your lifestyle, get a risk based on that. Ask your family history, get a risk on that. By integrating all of these things, they can tailor a circumvention treatment plan that works perfectly for you.
J. Nowak No, go ahead, please.
M We also see genetics playing at role other stages regarding screening for how aggressive a cancer might be and how best to treat for it. One thing that we do want to point out, though, is that the amount of data that exists today or that is used today by active admissions and pharmaceutical companies is very limited. As more data gets created in the medical system, as they begin to have more electronic medical records, as people participate in more clinical trials, we’re going to be able to develop much better guidelines. That for genetics to thrive and to really impact the care of cancer, we need to not just know good genetics, but we need to get good at clinical genetics, and that’s where patients can really begin to play a role.
J. Nowak Right. Now I know that being a prostate cancer survivor myself and having a few other cancers, I went out and … somebody and had the genetic or had my genome mapped, and I basically got no information that was at all helpful, which is what I expected. Can I assume that as the data matures, that this will become more and more important and more valuable and, in my case, I would get a lot more information?
M Yes, but it also depends how it was done. Did you get just genotyped, or did you get a full genome sequence? Was it a targeted test?
J. Nowak All I know is that I got five or six different phases. I can’t answer that question. They ran the standard test, I know the BRCA was run and they were having multiple cancers. There’s a syndrome that was looked at. I think more importantly going forward, what can we expect? Can this become something, a tool that will become a value to people like me?
Dr. Hershman Yes, I think there will come a day where that value does occur. What’s interesting is the technology has really progressed. When Danny and I started our PhDs it was $250,000 and a research effort to sequence a genome. By the time we left a genomic test was the type of thing we could order from a facility and it would cost less than $10,000 in a clinical setting, so the price has really dropped.
We’re now building up lots of data sets. We’re beginning to make some insights from them, but our abilities still are quite limited. These are early days in genetics. As we uncover more genetic causes of cancer and as we uncover more genetic predictors of drug efficacy and drug side effect, the amount that we can gleam from the same basic raw data is going to get better and better and better.
J. Nowak I’m a prostate cancer survivor and I would like to somehow find a way to contribute so that people in the future get more information. What do I need to do? How do I go about doing that?
Dr. Lieber Yes, that’s a fantastic question. We actually have recently started a startup called Genterpret, and our mission is essentially to try and connect patients with researchers; and the idea that patients who are willing, who feel comfortable to share some of their medical data can actually make a huge difference in advancing treatments, cares and diagnostic tests in order to further the field for the diseases that they care about. What we’ve set out to do is to create platform where patients can essentially for free get their genome analyzed, donate some information about their history and be able to contribute to science at the same time. We’ve actually set up a website that we’re using to launch this. Essentially what we’re doing is, so the website is myprostatehealth.us.
Essentially what we’re doing is we’re trying to gauge interest and to get individuals who would like more information about how can they contribute information that can help research to be able to do so. Specifically we’re interested in trying to correlate the drug that worked best for individuals with certain types of genetics, to try and limit side effects for individuals based on genetics and also to use genetics in combination with other factors, such as age and TSA, Gleason score, family history to enhance this prediction and to try and differentiate between those who may have aggressive versus indolent prostate cancer.
All of this can be done once a large data set is collected, but in order to do this we need engagement from our patients who are willing to donate some of their data. Again, the website is myprostatehealth.us. If you want to learn any more about our efforts, definitely check out the website and you can feel free to contact us. Our information can be found on that website.
J. Nowak If I decide to do it, what exactly do I have to do? I contact you. I’m willing to do it. What does it involve? Do I have to give you a sample of my blood? You take a scraping of my cheek? Do I get anything back from you at any point?
Dr. Lieber Yes, so it’s actually very, very easy and it’s convenient and free, but again, I have to reiterate that it hasn’t launched quite yet, and we’re in the process of getting support in order to do the study; but in order to get support, it’s important to know that patients are actually engaged and willing to contribute to this type of research.
What it is is essentially you would send the patient a simple spit kit from them to either swab their cheek or you can spit into a tube. The spit kit would then be sent back to us where after a couple months, two months, it would be analyzed. The individual would log into a system where they can enter any information that they would like. We also request access to certain elements of a patient’s medical record in order to get a sense of the course of treatment and also whether there’s a family history and other very pertinent details that can be used to correlate with the genetics in order to make discoveries that can advance care.
J. Nowak I see. Will I ever get any information back that once you’ve done this analysis, or is that asking too much?
Dr. Hershman Yes, you absolutely would … generates genetic data about individuals. We would hope to share it with everybody. We’re definitely going to share … data, but we’d also like to share analyses of it. It’s a little bit tricky because the FDA hasn’t clearly made a position as to for how these tools can work, but we’ve already actually made a prostate cancer risk calculator that as far as we know incorporates more locations in the genome than any other test.
For Caucasians we use 59 different data points, but we would certainly release your raw data and, at a minimum, guide you to websites that you could use to learn more about it. We hope to build an entire ecosystem of tools for individuals, so that everybody can begin to learn more about their health and their ancestry through their genetics.
J. Nowak That sounds absolutely terrific. Your web page is myprostatehealth.us. I think it’s something worth supporting. I’m actually going to suggest that you speak with Darryl, who was on earlier, about perhaps being able to post something like this on our new prostate cancer research funding site called Start a Cure, where we’re finding ways to support different types of research and asking people to do that. This may be well a different type of support, but something that’s just as important.
Actually, because we are coming to the end of our call, so I’d just like to try to bring together just a couple of points to make sure that we are all together with it. Cancer really can often be a result of a genetic mutation and, of course, this mutation could be one that you’re born with or what we didn’t talk about, but we also know that mutations happen just by living life. That we acquire these mutations and so what we’re trying to do now is to learn about these mutations through the various tests that exist and the work that you’re trying to do going forward and correlate them with certain diseases.
Currently we can look at these genetics to offer us a way to evaluate a risk that a man may have for prostate cancer, or people in general for other cancers, and then hopefully be able to take steps that would allow that person to hopefully minimize these risks. We also can gauge the aggressiveness of a disease and allow us to inform better treatment decisions, so that men don’t in prostate cancer need to get over treated when their cancer is not aggressive, and obviously those men who do have aggressive disease get treated.
It’s also, what the other exciting thing is it can better inform us as to what treatments may work for us, so that we don’t need to go through the expense, economic expense, or the pain and suffering of taking a treatment that is not going to help us and may allow our disease to progress and set us back even farther.
That’s how I summarize it. I don’t know if you have anything you want to add that I’ve missed.
Dr. Lieber No, that was a great summary. I guess the only other point to add is that genetics plays a role, a large role in disease, but it’s also not the whole picture by any means. Ethnicity, age, diet; there are many environmental factors that can also play a role. It’s important to keep that in mind as well; but genetics, we are incredibly excited about the potential that it holds to really revolutionize the way that treatments are discovered and the way that treatments are prescribed. We encourage everyone to learn as much as you can and if you have any questions, feel free to reach out to us. We’re happy to engage anyone about this topic.
J. Nowak Terrific. Thank you so much. I appreciate the time and I really appreciate the work that you are doing on our behalf. With that, I’d like to say goodnight to everyone.