Tag Archive for: prostate cancer genetics

Do Prostate Cancer Genetics Differ in African Americans?

Do Prostate Cancer Genetics Differ in African Americans? from Patient Empowerment Network on Vimeo.

Do the genetics of prostate cancer vary in African Americans? Expert Dr. Isaac Powell from Karmanos Cancer Institute discusses what research has shown about gene expression and what occurs in the body in African Americans versus European Americans.

[ACT]IVATION TIP

“…patients need to take charge by asking questions about the therapy. Again, ‘is it going to cure me, and is the chemotherapy going to cure, immunotherapy going to cure? If not, how long do we think that I will live?’ That’s a good question, that I’d like to know if I were a patient.”

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Transcript:

Lisa Hatfield:

So, Dr. Powell, I just read a bit about your really impressive research, particularly with regard to the biology and genetics of prostate cancer. Can you provide an overview of your research focus on how prostate cancer impacts African Americans in comparison to other ethnic groups?

Dr. Isaac Powell:

Yes, I would certainly love to do that. In 2010, we found that the cancer grows faster among African Americans compared to European Americans. And those are the terms we use now, as opposed to Black and white. In science, we use those terms. And so at that point, I thought that this may be driven by the genetics and biology. So in 2013, we used what now has been considered the artificial intelligence.

We use bioinformatics, which is computational biology, and gene interactive and network analysis to evaluate the cancer tissue. And so at that point, we identified, and we asked the question, are there genetic differences between African Americans and European Americans? And what they found were driver genes, driver genes being the genes that drive the cancer, that make the cancers carry out a function, a mechanistic function, as opposed to passenger genes that are just associated with the cancer, just as in a car, the driver is the one that controls the car, the passenger sits there. These passenger genes, yes, they’re associated with aggressive cancer, but they have minimal or no function. The driver genes are the ones that are controlling the cancer, the function mechanism of the cancer progression. And so we identified in our analysis 21 genes that were different between African Americans compared to European Americans, different in terms of the expression of the disease, not different genes, but different expression of the genes.

What we found is that African Americans have a greater expression of inflammatory genes and transcript genes. And I’ll be more specific about that in a moment. Whereas European Americans had a higher expression of lipid metabolism genes. Those are genes that are associated with fatty acids as well as unsaturated fatty acids, specifically omega-6 as opposed to omega-3. But there is a connection between these two gene interactions at one particular molecule called tumor necrosis factor. And this gene then interacts with both the lipid metabolism genes as well as other inflammatory cytokines. And the genes that we found that were more specific in among the inflammatory genes were the pro-inflammatory cytokines, and those were IL-6 tumor necrosis factor, IL-8, and IL-1B as well as CXCR4.

These are what are called pro-inflammatory cytokines and chemokines. And they carry out functions that cause the cancers to invade. First of all, the cancer initial is cancer cells are stuck together. We call them adherent. They have to come apart before they can spread and go elsewhere. Well, these genes cause that it’s called epithelial mesenchymal transition. And once that happens, they’re capable of being transferred to distant sites such as the bone. And they also cause increased blood flow to the cancer. They also cause the oxidative stress that is driven by a molecule called reactive oxygen species.

And we’ll come back to that particular molecule because that’s important. Once it causes the oxidative stress, this causes DNA damaged repair genes to develop as well as mismatch genes. This mismatch means there are gene molecules that are stuck together, and there is an order. This order is upset by this particular oxidative stress, and those are mutated once they are repaired, and they impact on the mitochondria, which is a molecule in the cell nucleus that controls the chemistry of the cell.

And then this activates cancer stem cells, which is really important. And this is where we are going now with the cancer research. So TNF, the tumor necrosis factor IL-6 and IL-8, and the IL means interleukins. That’s what that stands for. They activate that pathway, the oxidative stress pathway. They also individually activate other pathways that lead to cancer stem cells. And I mentioned cancer stem cells because that’s the reason why chemotherapy and immunotherapy and all the drugs that we’ve used don’t work because the cancer stem cells undergo mutations and these mutations change the character of the cell. 

And that’s why the cancer cells resist that after a certain period of time, now these drugs will work and prolong survival, but they do not cure them because of the cancer stem cells. And so the cancer stem cells, in summary, are driven initially by the pro-inflammatory cytokines. So my research currently is to, well, how do we inhibit these pro-inflammatory cytokines? And that’s where we are now trying to develop a drug. We’re at the stage of mouse at this time, mouse biology and testing the drug in mice, not ready yet for human testing. So that’s where my research is headed, and I believe that that is going to work if the drug works.

Lisa Hatfield:

So just a follow-up question to that is, as a if I were a patient of yours or a family member, I might ask, so with your findings, do you think that this could lead to a cure, for example, for advanced prostate cancer?

Dr. Isaac Powell:

Yeah. I hate to use the word cure. The word I use is that we, our goal is to eliminate death from prostate cancer. That’s the term I prefer, because when we talk about cure, we have to know what causes it in order to really be certain as we are curing it. Because I don’t know whether what we’re doing is going to eliminate death, but that’s our goal. So I don’t like to use the word cure, because that’s the magic word and everybody gets excited. So I don’t want to get people excited too soon. So that’s where I am with my research.

Lisa Hatfield:

Well thank you so much for that. And do you have an activation tip for patients for this question, Dr. Powell?

Dr. Isaac Powell:

Yes. I think that, again, patients need to take charge by asking questions about the therapy. Again, is it going to cure me, and is the chemotherapy going to cure, immunotherapy going to cure? If not, how long do we think that I will live? That’s a good question, that I’d like to know if I were a patient. In fact, I’ve had prostate cancer and bladder cancer, so mine was early, so we didn’t get into those kinds of questions. But I like to know whether is this going to be something soon or later? Nobody can tell you when you may pass away from any cancer. I never give a patient any time. If they ask me, “Well, am I going to live six months or three years?” I don’t know. Because everybody’s different. Everybody responds differently to these particular treatments. So, but ask the questions as specific as possible that you’d like to know about the treatments, because there are several treatments, and there may be many answers.

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What Is the PROMISE Study for Prostate Cancer Patients?

What Is the PROMISE Study for Prostate Cancer Patients? from Patient Empowerment Network on Vimeo.

Prostate cancer patients may have access to participate in prostate cancer studies. Dr. Heather Cheng from Seattle Cancer Care Alliance shares information about the PROMISE Study that she’s involved with and what the study examined in prostate cancer genetics.

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Transcript:

Dr. Heather Cheng:

The PROMISE Study is a study that I’m conducting in partnership with my colleague, Dr. Paller at the Johns Hopkins and other collaborators throughout the United States, and it’s a study to help men with prostate cancer understand their genetics. We know that there are many people who have prostate cancer who have genetic risks of prostate cancer, maybe they inherited a risk factor, but they don’t know about it, and this is important to know because now we have targeted or precision treatment options on additional toolboxes, treatments exciting treatments for those patients, but they may not be aware of it if they don’t know about their genetics. And so one is, it’s increasing the knowledge, and then also it may have important implications for the relative, so sometimes those genetic factors are shared and that information can also be life-saving. So the study is really easy, actually, patients who are interested or people that are interested who had a diagnosis of prostate cancer, go to the website, which is www.prostate cancer promise.org, and then they can read about the study and they can enroll on the web or by the Internet, and then they are mailed a saliva test or kit, and then they spit into the kit and then mail it back, and then they get a medical-grade genetic testing report back that test 30 genes that are associated with cancer risk. 

So some of those are prostate cancer, but then men who have certain mutations that we’re particularly interested in will be invited for long-term more…more long-term follow-up in all patients who participate can get a newsletter where we sort of inform them about the newest, latest, greatest things and prostate cancer. And so I think it’s really exciting because it’s increasing the ability and access of patients to genetic testing, but then also leveraging our web-based information platforms, just like this one, is to advance education and make sure we’re getting all of that excitement and opportunities out to patients even if they live far away from some of the biggest cancer centers, we want to make sure all patients have access to that knowledge.

Prostate Cancer Treatment Tools and Advancements

Prostate Cancer Treatment Tools and Advancements from Patient Empowerment Network on Vimeo.

What’s the latest in prostate cancer treatment tools and advancements? Dr. Heather Cheng from Seattle Cancer Care Alliance shares information about areas of prostate cancer research that have experienced recent advancements.

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Transcript:

Dr. Heather Cheng:

I think it’s a really exciting time. I think there are a lot of advancements throughout prostate cancer. I think one area of importance is early detection, but we also have newer imaging platforms, meaning the way, and we can discover where the prostate cancer is, is advancing through new types of PET scans that we didn’t previously have. And then my own kind of research which is near and dear to my heart is talking about genetics and what we have learned about the genetics of the risk of prostate cancer, but also how the genetics of the cancer itself, which sometimes is inherited, and sometimes isn’t can help us plan for better treatments for patients.

Prostate Cancer Genetic Testing and Family Testing Guidelines

Prostate Cancer Genetic Testing and Family Testing Guidelines from Patient Empowerment Network on Vimeo.

What do patients need to know about prostate cancer genetic testing? Dr. Heather Cheng from Seattle Cancer Care Alliance shares information about genetic testing, testing guidelines for those with a family history of prostate cancer, genetic counseling, and when it’s important to share family medical history.

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Transcript:

Sherea Cary:

Is it easy to get the genetic testing, and if you have a first-degree relative, if you had a father who had prostate cancer and your son, is it easy for them to get the testing, and do you recommend it?

Dr. Heather Cheng:

Yeah, I think that’s a question that I think it’s becoming easier, it is something that I think it’s important for people to understand what it can and cannot do, so if there is a strong family history of prostate cancer, for example, it is best to start with the person in the family who has cancer, if we were talking about genetic testing, if that’s possible. If it’s possible, testing that person, because if they have that marker, then we’re more confident that that’s important for the family, it’s sort of…if that person doesn’t have it, then it’s much less likely that the children or the relatives who don’t have cancer will have it. So I guess thinking about the person who has cancer and then also sharing with the family, sharing what the doctor is a family history of cancer.

But I guess one of the things that’s really interesting and I would guess, I would say challenging but exciting in the field, is that historically, we’ve had a reliance, or we’ve needed to do genetic testing through genetic counselors. And genetic counselors are professionally trained individuals who can answer questions about genetics, and sometimes patients or persons, people have a lot of questions, maybe they are not sure they want to do it, and so if they’re not sure that it’s important to get them the information so they can understand what the testing is about and then feel good about proceeding with testing. I think there’s a lot of value to knowing about somebody’s genetics, but there can be questions and concerns, and so we want to make sure every person has the chance to do that.

We have studies, and more and more, I think there is availability of genetic testing and people can do genetic testing through blood test or a saliva test, and the other thing that’s really important to understand is that there’s kind of two major classes of genetic testing, I would say, one is what I would call recreational for fun, and those are tests like 23andMe or Ancestry.com, where you’re trying to maybe you pay some amount of money and you want to know where in the world your relatives are from. That’s more for fun, it’s not really useful for medical purposes, if you’re thinking about genetic testing for how to manage your medical care, you might want to talk to your doctor about it, but there’s a different set of tests that are really medical-grade, and they shouldn’t be confused with each other because they have really different purposes. One is more recreational and one is, we need the quality to be much higher because we’re gonna use this information for your care, and we want to make sure is the sort of standards are a lot higher, and so for example, I have a study with my colleague, Dr. Paller at Johns Hopkins, where we were offering then we’ve met any type of prostate cancer, so any history of prostate cancer, and they don’t necessarily have to have a family history of cancer, but we would ask them about that, and if they’re interested in participating, then they get mailed, they can enroll at prostate cancer promise dot org, and then they are mailed us a Levite, and that test is a medical grade test that’s not one of the recreational tests, that one is, it is covered free of cost, so there’s no cost to the patient, and then there’s also an email and informational hotline if there’s more questions and somebody wants to, you know, learn more about it before they proceed. So that’s one way that we’re trying to expand the access of genetic testing to patients and their families.

Sherea Cary:

I have one more question. When we talk about family history, does that mean we have to have one or two generations or just one generation, how many generations qualify for a family history?

Dr. Heather Cheng:

Yeah, that’s a great question. I think a couple of important points. So, family history is really the available information that you have, and sometimes people have a lot of information about multiple generations, and sometimes they don’t, and I think whatever you have is important, and if you don’t have all of it…that’s okay, but the important things to think about are, do you know about any family history of prostate cancer, but…that should be on both sides of the family. Sometimes people will think, “Oh, if it’s only on my father’s side, should I only think about it on my father’s side because it’s prostate cancer” which is a male cancer. But actually, it’s really important to ask about both sides, because maybe your mom’s dad had prostate cancer, or maybe your mom’s brother had prostate cancer, that’s also really important to know about, and then some of the other cancers are also really important, such as is their breast cancer and the family, and is it on the mom’s side or the dad’s side? And if it’s known, kinda how old was the person when they had that cancer, where they’re in their 50s or where are they’re in their 80s.

So those kinds of things, if it’s known and many people don’t know all of these details, then that’s okay, but if you do know it, then it’s important to share it. And I think sometimes there are relatives who are a little less comfortable talking about their health. But if you think if there’s a culture of saying, “This information might help my kids or my grandkids to share that with their doctors and then think about their own cancer screening more proactively,” then maybe that will be an incentive to sort of open up those dialogues, I know sometimes it’s hard to talk about cancer diagnosis, but it can be life-saving.

How Is Genetic Information Used for Prostate Cancer Treatment?

How Is Genetic Information Used for Prostate Cancer Treatment? from Patient Empowerment Network on Vimeo.

Prostate cancer can impact patients differently depending on their risk group. Dr. Heather Cheng from Seattle Cancer Care Alliance explains how genetic information is used in prostate cancer treatment and other factors that can impact patient outcomes.

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Transcript:

Sherea Cary:

Can you speak to how you and your colleagues are using genetic information to help with the treatment and understanding prostate cancer for different risk groups?

Dr. Heather Cheng:

Yeah, thank you that…that’s something that I think is following the lines of this idea of precision oncology or tailoring. Tailoring people’s management, either if they don’t have cancer and we’re worried about the risk of cancer, we can use genetic markers that we can test from saliva or blood to help understand that person’s risk of prostate cancer better, and in some cases, there are some families where there are markers or genes that run in the families that might increase the risk of developing prostate cancer, but also sometimes the same genes are increased the risk of breast cancer and ovarian cancer, and if they’re present, then it’s important to think about knowing that, getting that information, because then there are strategies that we can use to find it earlier and to treat it more aggressively and hopefully have much better outcomes in a much better likelihood of curing prostate cancer. But then also the other related cancer, so for men, this is really important because we haven’t previously been thinking about it in the same way, but that’s one example of how genetics can affect the thinking about the risk of prostate cancer. We know that Black men have a higher risk of prostate cancer to begin with, and we were beginning to understand why that might be.

Some of it may be genetic, some of it may be access to healthcare and knowledge, which we’re trying to help disseminate the knowledge here, and then sometimes it’s care delivery, so we want to focus on all of those things, but genetics are part of that.