The Impact of Molecular and Genomic Factors on Prostate Cancer Disease Etiology and Health Disparities and The State of Science on Diet and Lifestyle - Lorelei Mucci

January 24, 2023

In this conversation, Lorelei Mucci and Alicia Morgans discuss highlights from the 29th Annual Prostate Cancer Foundation (PCF) Retreat, including the immunogenomic landscape of African-American prostate cancer patients, a presentation by Tamara Lotan as part of the session titled the Impact of Molecular and Genomic Factors on Prostate Cancer Disease Etiology and Health Disparities. They also discuss the panel on the State of Science on Diet and Lifestyle in Lethal Prostate Cancer and Survivorship.

Biographies:

Lorelei Mucci, MPH, ScD, Professor of Epidemiology and Director of the Cancer Epidemiology and Cancer Prevention Program, Department of Epidemiology, the Harvard T.H. Chan School of Public Health (HSPH).

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts


Read the Full Video Transcript

Alicia Morgans: Hi, I'm so excited to be here with Professor Lorelei Mucci of the Harvard T.H. Chan School of Public Health. Thank you so much for being here with me today.

Lorelei Mucci: Oh, I'm so excited to be here. Thank you so much.

Alicia Morgans: Wonderful. I always value your perspective, and today I wanted to pick your brain on the amazing PCF Scientific Retreat that we are all attending, and would love to hear, what's exciting you at this year's retreat so far?

Lorelei Mucci: Yeah. Well, I think first of all, being all together and feeling the energy of everyone. I miss that so much. I think all of us have been craving to be together. There's something when you bring people together in a setting like this where you create new collaborations, think of new projects together, new ideas. The other thing is to see all the young investigators who've come on board PCF over the past few years. That's been incredibly exciting too. To see the types of research they're doing is really wonderful.

Alicia Morgans: They are so innovative and they're so enthusiastic. I think the energy, just being around them, as someone who perhaps is older or more tired, I don't know which, but maybe both, but they are so excited to be here.

Lorelei Mucci: They are. They are.

Alicia Morgans: And really to see everyone, like you said, in person.

Lorelei Mucci: Yeah. So that's been fantastic.

Alicia Morgans: Wonderful. So from a science perspective, I do have to set the stage and say we're only about a day through the entire retreat, so this is not a commentary of the entire thing. But so far, what has been the thing that's excited you the most?

Lorelei Mucci: Yeah, actually, this morning there was a fantastic session to try to understand why there are these strong racial disparities in prostate cancer. And so there was a wonderful session that really focused on looking at biologic differences that might help understand the underlying causes and of some of the disparities that exist.

In particular, there was a wonderful talk by Dr. Tamara Lotan from Johns Hopkins, where she has a really incredible patient cohort of 200 individuals who identify as Black or African American, and the other 200 who identify as White. First of all, she took a broad look at methylation data in the tumors as well as the adjacent tissue, and was able to infer something called copy number variation in these, and show these dramatic differences in the tumors of individuals. Even if you account for differences in grade or stage, you still see these really dramatic differences related to immune-related pathways. So that was really exciting.

Alicia Morgans: That is so exciting. And were they just differences, or was one up-regulated or was one lower?

Lorelei Mucci: Yeah. So in the Black men, or African American men, there were two genes, and I think the data haven't been published yet, so maybe I won't say what these are.

Alicia Morgans: Sure, of course.

Lorelei Mucci: But there were copy number changes in two specific genes at the tumor level that were really strongly higher in Black men. And then what was also interesting was that she showed at the germline level, so the inherited basis for these two genes, you also see increased expression of these same markers. So that was really interesting to see. So if these are prognostic, it could explain some of the differences and why there's such a high rate of mortality from prostate cancer in Black men.

Alicia Morgans: I think it's so interesting too, the way, from my perspective, it reinforces the validity of the finding in the tumor if we also see some difference in germline that could then predispose to us seeing larger differences perhaps in the tumor, because we are of course, all starting off as the genes that we have throughout the entire body, and it's within the tumor that we see then maybe furthering of some of these mutations. So seeing those differences, even at germline level, to me is really validating. It's really interesting. Wonderful. Well, so that was exciting. Wonderful. What else excited you? And actually, if you could speak to your panel. You hosted a wonderful panel.

Lorelei Mucci: Yeah. No, first I'd like to just really acknowledge that the Prostate Cancer Foundation has always been a big supporter of thinking about how the roles of lifestyle and diet might be really important and complementary to some of the studies about new drug development or new biomarkers.

So we had a great panel. We had four really thought leaders in the field from different backgrounds and trainings. We had two fantastic cancer epidemiologists. We had a urologist and we had an exercise physiologist. So really bringing in different perspectives. We had everything from clinical trials to epidemiology research to even some experimental studies, and said, what is the state of science? What do we know really could benefit individuals with prostate cancer, both for survival and survivorship? So I think it was really a great session.

Alicia Morgans: I agree completely, and I love the way that you really went through some of the overlap in nutrition in particular, and some of the risk factors that are similar for prostate cancer and for cardiovascular disease, but then the diet recommendations also have a lot of overlap, so there's a way to combat this. And it was so fascinating to hear people who have been thinking about this for a long time, and have done such an amazing body of work, giving some clear guidance of things that we can do now and today to actually potentially make a difference in these areas.

The final thing I would just commend you on is that this area, diet and nutrition, is one area where we can actually potentially improve the health related to prostate cancer, but also improve the quality of life of this individual on such a level. I wonder if you have thoughts about that?

Lorelei Mucci: Yeah, no, I absolutely agree. I think one of the factors we talked a lot about yesterday in our panel was around physical activity, and I think that's the perfect factor that really has such a broad health effect. So one of the panel members talked about the large reduction in mortality from prostate cancer, but also, regular physical activity and even things like brisk walking can improve cardiovascular health, improve things like sleep, which are big problems for individuals with prostate cancer, improve fatigue, but also emotional health as well, which we're really starting to learn is a really significant health effect for patients living with prostate cancer.

I think the other part that we talked a lot about that was really interesting was these are types of things you can do not only if you're a person living with a more localized, low-risk prostate cancer, but even in individuals who have more aggressive disease or whose cancer has progressed to metastatic cancer. There's things that really can improve their survival and their survivorship.

Alicia Morgans: Absolutely. And some things can improve one or the other, but these things can actually, in most cases, improve everything. So that's really, really exciting. So if you had a final take-home message, your thoughts from this PCF annual Scientific Retreat, what would that be?

Lorelei Mucci: I think one of the wonderful themes that's come through many of the talks, as well as some of the meetings that we've all had, is the importance of bringing diverse backgrounds and perspectives together to really tackle this disease. And I think when you think about different disciplines coming and working on a problem together, the sum of those people working together is so much greater than the individual part, and I think that's something thematically that we have forgotten about during the pandemic. We are a little bit more isolated. But being together and working across disciplines in a team science approach, and particularly bringing those young investigators in, which PCF has always been such a big supporter of... So I think that's something that I'm really going to take home from this meeting.

Alicia Morgans: I'm sure you will, and I'm sure we're all going to go home newly motivated and really renewed in our passion to attack this disease, and to your point, to really collaborate and enjoy what we're doing as we do it. So thank you so much for your time and your wonderful expertise.

Lorelei Mucci: Thank you so much.

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