Dr. James Mohler and Dr. Elizabeth Fontham Video (Text Version)
Title of Talk: North Carolina–Louisiana Prostate Cancer Project
Thomas LaVeist, PhD.; Johns Hopkins University
This—this plenary session is on the North Carolina–Louisiana Prostate Cancer Project or PCaP; we have two presenters today representing the two institutions that are doing the project. It’s a collaborative project between the two states. And we’re going to do things a little bit differently. They’re going to both come up and present together and sort of do a—I don’t know who is the straight man and who is the color commentator but they’ll—they’ll come up together and do a presentation. Their bios are—I believe you have them in your programs, so I won't read them all—the entire bio but I’ll just say a few things about—from the bios of each of our speakers.
Elizabeth Fontham is the Professor of Epidemiology and Dean of the School of Public Health at Louisiana State University Health Sciences Center in New Orleans. And also she is Associate Director of the Stanley S. Scott Cancer Center and a Senior Consultant Epidemiologist to the Louisiana Office of Public Health. Her collaborator is James Mohler, who is Associate Director and Senior Vice President for Translational Research and Professor of Oncology and Chair of the Department of Urology and founder of the Prostate Program at Roswell Park Cancer Institute in Buffalo, New York. He’s also a member of the Lineberger Comprehensive Cancer Center at the University of North Carolina. And they’re going to be speaking about the North Carolina, Louisiana Prostate Cancer Project.
James Mohler, M.D.; Chair, Department of Urology, Founder, Prostate Program, Professor of Oncology, Roswell Park Cancer Institute
Thank you. Thank you very much. I’m going to start here and then Terri will join me and we’ll go back and forth with the different parts of the presentation that we’re both most knowledgeable about and hopefully one of us will be knowledgeable about every aspect of it. This is a very different project that was one of the two consortia founded by the Department of Defense Prostate Cancer Research Program and I’m very proud to stand here because most of the Integration Panel did not think this could be done. We were not sure whether you—the urologists in North Carolina and Louisiana would let us study their patients and most especially we were not sure whether men newly diagnosed with prostate cancer would participate. Obviously since I’m standing here we have been successful.
So let’s take a look at this; in 2002 when we originally proposed this study, what did we know about racial differences in prostate cancer? You have to think all the way back to then when the first studies were just being published that there was in fact a racial difference in incidents and mortality. At that time, it was shown that the incidents was 1.6 times higher in African Americans and the thing that is particularly interesting to me is why is it that when an African American man is diagnosed with prostate cancer is he 2.4-times more likely to die of it.
Now compared to Caucasian Americans, African Americans have more aggressive prostate cancer. At that time it was thought they made poor treatment choices or were offered only some of the treatments available and so that they underwent inferior treatment for their prostate cancer. And they more often presented with incurable prostate cancer and it was thought because they were reluctant to participate as a group in early detection programs.
So our colleague, Merle Mishel who has been instrumental in this program had published at that time on racial differences in healthcare system interaction. And this—this study mostly illustrated that there were very few inherent differences in African versus Caucasian Americans, and we thought at the time that this should not be used as an excuse for the racial differences in prostate cancer mortality. What was interesting, at a very carefully done study was that, in general, Caucasian Americans preferred to relate with their doctor regarding treatment decisions on a—in a data-driven way whereas African Americans tended to want—want their data more as a shared personal experience.
So shortly thereafter she published Race Concordance Appears to Improve Satisfaction and I just probably told you why. There was some inherent mistrust in the health care system, and I being the kind of—kind of brought up in the Midwest white guy had never heard of Tuskegee. And I learned in 2002 how important that is in the African American community. So the benefits of an outreach program that was nursed, telephone-delivered that we established in 2000, were proven to be that there was a decreased rate in the duration of incontinence and impotence in men who became more knowledgeable about prostate cancer.
This—this also empowering these men with knowledge improved their communications and therefore their satisfaction with their physicians and the men all felt regardless of race reduced depression, fatigue, anxiety, and confusion, and this leads to the concept of uncertainty—uncertainty that is true about every aspect of prostate cancer can be harnessed so that it can empower men instead of intimidate them and I should say and their wife.
So we also had at our hands preliminary data generated from my laboratory that prostate cancer may be more common and aggressive in African Americans because of biological differences in the host or the host cancer. So we had just conducted a pilot study published in the Journal of Urology that—that demonstrated in a—in a study of only 50 radical prostatectomy specimens that African American men had a higher expression of the androgen receptor in both their benign prostate and—and even to a greater degree in their cancer. So it may be that an African American prostate is a prostate that is revved up and ready to respond to some type of dietary or environmental action that will make it more likely to undergo malignant transformation.
So we asked the simple question—could it be not only the androgen receptor but the amount of androgens available to that androgen receptor? The most common explanation for androgen receptor over expression is it’s being stabilized by its ligand testosterone and at that time Dr. Ross who has since died had published that serum testosterone levels were higher in African Americans. But case control studies said this wasn’t true. And when you go back to his original research, it was actually conducted in African American college students in Louisiana and this difference in serum testosterone that’s in all the textbooks does not persist in older men and cannot be used as a reason for the racial differences in prostate cancer aggressiveness. But being the eternal skeptic that I am, I said well maybe it’s different at the tissue level because where we saw the androgen receptor expression difference was in the tissue.
So we had stored away—you can add this up—110 frozen prostate specimens of cancer and benign prostate from African American and Caucasian American men, and we measured all these using radioimmunoassay asking the question of—were the testosterone levels going to be higher in the tissue of African American men. And to make a long story short, there was no statistically difference in any of the things we measured except for androstenedione, an adrenal androgen that back then we didn't know could be important and SHBG, so that SHBG, though higher in the prostate of African Americans it binds testosterone and yet the testosterone levels were the same.
So the conclusion at the time was that we had tissue levels of testosterone and DHT that were the same in the two races. We didn't think the SHBG made any difference but we knew that there was more androgen receptor in the prostate of African American men. So we thought that the higher androgen receptor levels may allow racially similar levels of tissue androgens to for some reason cause more aggressive prostate cancer in African than Caucasian Americans. So it’s with this knowledge in 2002 that we went forward to the DoD with this crazy idea—Terri.
Elizabeth Fontham, M.P.H., DrPH; Dean, School of Public Health Louisiana State University Health Sciences Center
Notice Dr. Mohler gave me just the crazy idea parts of this discussion. So the overarching goal as we turn to PCaP as opposed to the preliminary data of this multifaceted consortium was to generate data that could be used for evidence-based decision making for the most effective best use of public health resources as to whether we should alter the critical patient and health care system interaction or alter patient exposures and response to exposures where they were modifiable or to impact and make changes in tumor biology where that was possible or some combination of these three areas.
In particular, to reduce prostate cancer mortality but specifically prostate cancer mortality in African American men where the disparity was particularly clear; our hypothesis—those of who you who were lucky enough to go to Dr. Mark Litwin’s presentation last night, where he talked about access to care in his keynote address, he noted that even access to care is a complicated issue. Simply being able to walk in the door doesn’t guarantee equal timely, equal and high-quality access. So it’s no surprise that our hypothesis was multifaceted. The mortality rate from prostate cancer is more than two-fold higher in African Americans compared to Caucasian Americans and that is due to racial differences we hypothesized in these three areas—interaction with the health care system, diet, and biology of the host and/or characteristics of the tumor.
So when we look at the details of how we’re going to go about making these tests of our hypothesis on three levels, let me tell you some of the variables that we’ll be looking at. In level one, racial differences in the interaction of the health care system will be evaluated by examining early detection behavior; socio-economic status; attitudes, beliefs and knowledge; health care access; patient and physician communication; patient decision making; alternative treatment use; and treatment choices.
So level two—racial interactions in host biology may affect prostate cancer aggressiveness due to genetic, environmental, or gene environment interactions. Racial differences will be sought in the area of diet, and we have upfront put emphasis on antioxidants and fat consumption but we have a complete dietary history, pre-diagnosis diet and so we can do much more than those two areas. Serum androgens, exposure to carcinogens, expression of prostate cancer susceptibility genes such as androgen metabolism pathway, detoxification, DNA repair, and hereditary prostate cancer genes, and serum protein profiles associated with the aggressive prostate cancer phenotype.
The third level—racial differences in tumor characteristics will be examined. And to do that, we look at tumor extent, the clinical stage, and serum PSA as a tumor volume surrogate, tumor differentiation, high Gleason grade and tumor growth rate, apoptosis in cellular proliferation, also expression of androgen receptor, androgen receptor co-regulators and androgen-regulated genes and stem-like cells.
So to do all this we have to have a substantial study population and so I’d like to tell you a little bit of the men who chose to be in our study who were volunteers, and we owe them a huge debt. Unlike the project we heard about in California, this study involved no intervention, so the men who agreed to be a part of our study had no personal gain other than the knowledge that they were contributing to a better understanding of prostate cancer. The interview was more than 3 hours long, and they voluntarily agreed to give us eight tubes of blood, have adipose tissue aspirated from the abdomen, urine, nails, hair, you name it—we asked for it and the men were wonderful to give it to us. We had approximately equal numbers from Louisiana and from North Carolina, approximately 1,000 in both states, 50% African American and 50% Caucasian.
In Louisiana we began with 13 parishes, which is what we call counties in Louisiana, and Louisiana was a wonderful contrast to North Carolina for this project because African American men in Louisiana have among the lowest rates—mortality rates for prostate cancer of any other state in the Union for African Americans. Obviously their rates are much higher than Caucasian Americans in Louisiana. North Carolina on the other hand, same number of men, 50/50 African American and Caucasians but in North Carolina the men there have among the highest mortality rates in the country and just to show you that these are the study areas. This shows a 25-year period. Blue is a low rate; red is a high rate. And you can see that when the U.S. mortality rate was 47 deaths per 100,000 men, African American men, Louisiana, the comparable mortality rate was 42 and in North Carolina it was 55. So if we’re going to understand differences it’s good to know what’s happening in low risk areas, what’s happening in higher risk areas.
This is the North Carolina study area, and you will see a little bit about it when I show you that over 4,000,000 pounds of tobacco are grown there every year and they raise over 100,000 hogs. Now this is not a good public health advertisement since the hogs contribute to high-fat diet and tobacco is the number modifiable killer in the country but the Louisiana slide is not much better. This was our study area and you will see crawfish playing fiddles and Mardi Gras that made it almost impossible for me to get out of town on Wednesday. And with that I’ll turn it over Dr. Mohler.
James Mohler
So you can see there’s a great deal of variability in not only the prostate cancer mortality rates, but also what men are subjected to in the two states. So we put together a group of institutions and I always like to make fun of my friends at Harvard, the Duke of the North. We probably spent more time dealing with intellectual property issues and budget with Harvard than all the other centers put together, but Howard had mentioned it earlier during the consortium talk, it was a real challenge in 2002 to deal with intellectual property issues. And—and we managed to—to do that.
So we have an organizational structure that is arranged around the levels that Terri mentioned, the green, the pink, and the yellow but what you forget about is we have to have an entire infrastructure for doing a study like this. And so we have an epidemiology corps to make sure that we do everything properly—that this is a properly done population-based study. Then we have to have all our blood and tissue managed somewhere in the corps and then we have to have our tissue microarrayed, sectioned, and available for study coming from another corps and then the most important one is the administrative corps to deal with all the consent issues, intellectual property, et cetera, et cetera.
So the home visit averaged about 4½ hours in length. Terri said what it was composed of. If you have really good eyesight you can read all that stuff we collected, and importantly almost all the patients gave permission to have their medical records abstracted so that we have very granular data that can annotate clinically these important biospecimens and the questionnaire data collecting during the home interview.
So we managed to complete accrual of 2,258 men, all of whom were home visited by our nurses. The North Carolina study visits ended in November of 2007; the participation rate in the two states was that consistent with any population-based study. The men were willing to participate as well as any other group of people engaged in this type of research. The Louisiana study ended a little later on the fourth anniversary of Hurricane Katrina to the very day, the last home visit was the fourth anniversary. The participation rates between the two states were similar and so there didn't seem to be any inherent bias in doing a two-state study.
Now what was very interesting; I’m just—I’m a surgeon and a laboratory researcher. I knew nothing about population-based research and boy have I gotten a lesson. So we had to first make sure that we had—did everything the same in the two states. We had reams and reams of data. We couldn’t have paper so we had to develop all these scanable forms. Now remember in 2002 this was pretty new technology. And things you don’t think about—it’s really hot in North Carolina in the summer and it’s much hotter in Louisiana, so we had to develop a specimen handling and transport system to keep all our specimens cool.
We had to pilot that to prove that since all the analysis was being done in the corps laboratory at North Carolina, we had to prove that we could do the initial preparation of the specimens in Louisiana and store them and ship them to North Carolina and get the same answers as if we had done the analysis in Louisiana itself. So we ran up incredible Fed-Ex bills and had to prove that this was possible.
We also had proposed to study the diagnostic prostate biopsies but that turned out not to be possible with community acquired prostate biopsies and now we’re even struggling with community-acquired radical prostatectomy specimens. We’ve learned a tremendous amount about tissue microarray which again in 2002 was brand new.
And then most importantly, we were informed by our PCaP advisory committees and probably the most important one of these was our advocate committee—it’s been a recurring theme of this meeting; we would not have succeeded if it was not for the changes that were made in the PCaP study at its inception by becoming more sensitive to what was necessary to successfully enroll men in this study.
So we developed on the administrative level several very important documents that are all posted on our website, and we share freely with other people who are attempting to do research of this type. Now we had two natural disasters. I’m going to tell you about the first; it’s called HIPAA. We were just ready to enter the field, the week after HIPAA came down. We had to stop our study; it took one entire year to become HIPAA compliant. We had set up that our advocates were going to call the patients first and tell them about the study and encourage their enrollment and obviously we couldn’t do that. We had to change the whole way that we managed our data, we managed our consent process, everything about the study had to be changed. So the DoD hung with us during this 1-year period. And then the second disaster—
Elizabeth Fontham
Yeah; you can see what the second disaster was; 363 days after we went into the field, the levies broke in New Orleans and this particular levy is the one that let the water into the lower 9th ward where we are still experiencing some—some difficulties. The next slide shows the LSU Health Sciences Center, just a snippet of some of the buildings; the elevated walkway that you see there is very, very high, multi-stories off the ground, and if you can see the water line, you can see that it’s quite high and so of course the first floors of all the buildings were impacted.
And the final Katrina slide not to bore you to death was the inside of the School of Public Health and the black on the walls which is pretty hard to see in this particular slide is mold. We are now in our fourth set of offices since Katrina. If you think it’s hard to move a-program or a-lab, try moving a school four times, and unfortunately we have to move again in June, but I’ve been promised it’s our last move. Otherwise I can go into competition with the best national moving company there is.
So what was our response to this Katrina surprise? It was clear we had to suspend our operations in Louisiana. The investigators were out—out of the city and dispersed and many of the men who would otherwise have been in the project had relocated to Baton Rouge, to higher areas in Louisiana as well as to Houston and Atlanta. We needed to expand our study area in Louisiana obviously; our highest proportion of African Americans is in Orleans Parish and that has slowly recovered I’m happy to say; our population has over time come back to a large extent but not completely. But we really needed to have an additional accrual source and in North Carolina, in order to meet the timely goals with enough men and the distribution that we wanted in terms of 50/50 we had to expand the study area there as well.
And to do all that we needed additional funding. So what was the response of the—the Prostate Cancer Research Program of the Department of Defense? It was uniformly and totally supportive. They took us at our word that we could do what we promised to do and we were praying every night that we in fact could do what we promised to do and I’m happy to say that their trust in us paid off, because I think we have—we have a wonderful resource that is available not only to our research team and others in this country but internationally as well.
Our—in terms of the participation in this study, we had good rapid case ascertainment reporting by urologists but primarily pathology labs and—and hospitals in the study area. MDs gave us permission to contact their patients; 93% of their patients. Jim already mentioned the 63% study-wide participation rate, which is quite good these days for a population-based study. And the men agreed, 92% up to 99% on making biospecimens available to us. The 92% low was the adipose tissue aspirated from the abdomen and the 99% were for a number of specimens including urine and hair and nails and the ones that you might suspect. Almost everybody said yes. Virtually 100% of the men who agreed to be in the study gave us permission to obtain and review their medical records and 97% contacted for future studies.
James Mohler
So what’s somewhat unique to this study is that we took advantage of clinical data to differentiate the tumors by their aggressiveness, so we called this clinical aggressiveness. But we decided early on that we needed a more objective end point and so from all the biopsies we’ve determined the cellular proliferation rate and the apoptotic rate from which we can calculate a growth rate for each participant in the study. So we have growth rates on all of them. We’re doing the growth rates now from the radical prostatectomy specimens and you can see how potentially valuable that would be.
Now when we planned the study, we thought that 20% of patients would fall into the low aggressive, 20% into the high aggressive categories, and all the rest would be in intermediate. That turned out not to be true because the PSA was being disseminated throughout the male population at that time and so there was an increased frequency of detection of low aggressive disease so you see that the actual distribution was 50, 30, 20 which improved our statistical power.
So now we want to just review a couple of the publications. This one is the first in the prostate that describes the PCaP study and is now from 2006, so you can consult that for the details of what we’re talking about. Our most recent and high-profile publication is by Bill Carpenter, and this was published in Cancer last year and got a lot of national press attention. So this was an examination of racial differences in trust and regular sources of patient care and the implications of this knowledge for prostate screening use. And what—what we found is that the stage at diagnosis was similar between the races. But the Gleason scores were higher in African American men. Caucasian Americans were more regularly seen by the same physician, which was associated with greater trust in their doctors and in physicians in general.
Caucasians Americans were more likely to receive regular prostate cancer screenings and to get all their medical care at a physician’s office as opposed to an alternative health care location. Men without a prior history of prostate cancer screening were more often diagnosed with advanced and/or aggressive prostate cancer and when men of either race had established relationships with a health care provider, the differences in prostate cancer stage and graded diagnosis disappeared. So the solution to this problem has a lot to do with improving the interaction between all men and especially African American men and their primary caregivers. This would go a long way toward decreasing the racial disparity in prostate cancer mortality.
Now we have several newer studies that the DoD wanted us to communicate with you about—what’s coming right now. So the first one was actually mentioned by Dr. Xu in the earlier penetration about doing G-West SNP assay, and this is a report of G-West SNP in the PCaP population, a different population than what he discussed this morning. So 32 SNPs have been reported associated with prostate cancer in G-West of Caucasian Americans; 800 SNPs including these 32 and 35 flanking SNPs were genotyped in 417 African Americans and 455 Caucasian Americans from the PCaP study and then compared to publicly available controls.
So of these 32 SNPs, 13 in Caucasian Americans and only 4 in African Americans were associated with the diagnosis of prostate cancer. And of the 35 flanking SNPs only 1 in Caucasian Americans and 2 in African Americans were associated with the diagnosis of prostate cancer. So of the remaining 356, almost none were associated with prostate cancer in either race. But no SNP produced an AUC in ROC plots that made it sufficient for clinical use to stratify men for better use of early detection.
The second study is to me fascinating; this gets at the difference between genetic and self-assigned race. And so self-reported race is really a social construct; it’s often used to as a proxy for genetic ancestry even though the proportion of European ancestry among African Americans ranges in the literature from three and a half percent in the South Carolina Gullah population to 22.5% in New Orleans. So you can obviously see that we got a problem comparing North Carolina to Louisiana when there’s so much ad-mixture in Louisiana. So we used 50 ancestry informative markers or aims and structured software to estimate the proportion of African and European ancestry for each of 2,120 PCaP research subjects that we had high quality DNA on. The genetic diversity was greater in Louisiana than North Carolina and was actually found in both African Americans and Caucasians in Louisiana. So the message here is that ethnicity complicates race, and both must be considered in any attempt to understand prostate cancer health disparities.
Now the situation in Louisiana is much better discussed by Terri.
Elizabeth Fontham
This actually is not the Louisiana one; this—this is what we saw across the board in both Louisiana and North Carolina. Do you want to do it?
James Mohler
Yeah; oops. Here take your papers. Okay; so this is the Louisiana situation showing that 10.7% of African Americans have European genes in them. And in North Carolina you can see it’s only 8.3%. Among the Caucasian Americans in the two states, Louisiana Caucasians have 2.16% African genes and in North Carolina it’s only 0.07%. So this confirms differences in geographic distribution among the races between the two states. And here’s the reason; there you go.
Elizabeth Fontham
This illustrates the value of asking about both race and ethnicity. It’s not necessary to do a panel of 50 genetic markers of European ancestry and African American ancestry to understand that both biologically and certainly culturally there are differences that can be explained by asking about both. And you see this is just in Louisiana and among the men who reported—identified themselves as African American, 11 also identified themselves as Cajun ethnicity and that’s in the southwestern part of the state, a much larger proportion, 73 of the approximately 600 men identified themselves as also Creoles and just a few said that they were both of Cajun and Creole ethnicity.
And when we compare the proportion of the European genomic markers in those men with the African Americans who reported none of these ethnic groups we see significant differences for the Cajuns, for the Creoles, and for the combination of Cajun and Creole, anywhere from 20% to almost 50% versus 8.2% of the rest of the African men—African American men in the study. Hispanic ethnicity was not reported among the African Americans. But among the Caucasians, those Caucasians who identified themselves also as Hispanic ethnicity, they had a significantly lower proportion of European ancestry compared to the Caucasian Americans who reported none of the ethnic groups.
So we have another manuscript that’s under review right now and it was led by Joseph Su and it looks at obesity and prostate cancer aggressiveness. Certainly there is an open question right now of whether obesity or physical activity or diets high in fat are associated with risk of prostate cancer, with risk of dying of prostate cancer, or with tumor aggressiveness. The studies are inconsistent; that may be because there’s no association, that may be because there is a very modest association, and if you don’t have the sample size you don’t pick it up. It could also be because it’s apparent in one ethnic group and not necessarily another.
But what you can see here is when we look at body mass index that was measured by nurses at the time of interview and I will also say we got usual height and weight reported before prostate cancer was diagnosed because we were worried about changes, and we saw exactly the same thing—that as BMI increases from normal to overweight to obese to morbidly obese, the risk of aggressive prostate cancer significantly increases. It’s clearest in the Caucasian American men but when we compare African American men in each one of those weight groups with normal weight Caucasian Americans we see an even higher risk within each weight group of aggressive prostate cancer, and there is an increase with obesity but the increase is more modest there from normal weight to morbidly obese men than you see in Caucasian Americans. So yes; it’s likely playing a modest role, but it’s different in Caucasian men and African American men.
James Mohler
So we’re trying to dissect further the racial differences in patient satisfaction with their healthcare provider and this is a further look at the North Carolina cohort and this uses a very fancy statistical design. This is the work of Merle Mishel and her students called Confirmatory Factor Analysis that revealed that patient satisfaction was impacted by racial differences and contextual knowledge about prostate cancer but not the quality of the patient and health care provider interaction or interpersonal treatment.
This is an incredibly sophisticated statistical analysis that I don’t understand and I put this figure in here so y'all could see why I don’t. But the bottom line is that the second level of analysis is called SEM Analysis Structured Equation Modeling and it looks for the most important factors that explain the conclusions that were on the first slide. And you can explain 56% of the Caucasians’ problem with interaction with the health care system and 57% of the African Americans variation or problem with interaction by improving interaction with the health care provider—that’s true of both races; better access to care—both races; less traditional health beliefs—that’s African Americans only; and greater medical literacy—Caucasian Americans only. So you can see how you have to take anything you want to do to improve the interaction to—by race and I would hold even down to the individual. We’re making sweeping generalizations here.
So because interaction with the healthcare provider is important it only—it only though explained 20 and 29% of the variation in the two races, so this is less important. Perceived racism is important by both races. Physician trust—both races and better access to care, stronger religious beliefs were more important in African Americans than Caucasian Americans. So if you want to put your money as a health care system, you put it in the top; you really improve the interaction with the health care provider.
This is the last study we want to tell you about.
Elizabeth Fontham
In this study, we took a look at whole grain consumption in the diet, and we looked both at whole grain consumption, processed grains, and fiber. And you can see in this slide the odds of high aggressive disease—let me see if I can do the pointer—the odds of high aggressive disease go down as the highest consumption of whole grains occurs. This is in African Americans. We see the same thing in Caucasian Americans. And when we combine the two groups that 35% reduction of high aggressive disease, the probability of high aggressive disease is statistically significant.
One is tempted to say this means dietary fiber is protective. We did the same thing when we found out that high intake of fruits and vegetables reduce risk of lung cancer. Somebody saw beta-carotene worked in rats and concluded beta-carotene was what they were getting from fruits and vegetables. We subsequently did a study, a chemo-prevention trial with beta-carotene and found out that lung cancer not only was not prevented by beta-carotene but in smoker’s beta-carotene increased the risk, so we promptly ended that trial. And I use the we loosely; I was not a part of it, but it is a fascinating example of trying to attribute a whole class of foods or in this case grains from multiple different foods and say it’s X inside of it. Well we took a look at dietary fiber, and we did not see any significant protection associated with dietary fiber.
So what do we—what do we have with regard to end products from this study that you might be interested in? We have a repository for future use with plentiful and detailed clinical data, three hours worth of epidemiologic interview, biological specimens that we’ve talked about—tissue, microarrays and a coordinated aggregation of high and low risk persons.
James Mohler
So how are we making these more valuable? We have had funding by the American Cancer Society a follow-up study in North Carolina that is collecting outcome information and treatment information on all the participants. In Louisiana, we have an R15 to Christine Brennan that’s doing the same thing as a one-time follow-up. Getting work like this funded is virtually impossible, and I can't tell you how many unsuccessful applications there have been.
This type of outcome research though is rich for publication and that just lists the four papers that are—have been written and are under review right now just from the North Carolina Outcome Cohort. And then I have a DoD grant funded examining the androgen axis in the PCaP specimens.
Now all of you can access our website right there, and we have personnel who can guide you through interrogation of these biospecimens or the interview data associated with them. So I want to thank the Department of Defense as well as all our participants. The Department of Defense allowed us funds to prepare this grant; they then funded us initially with $10 million and then granted us the Hurricane Katrina cost extension. So what you just saw is a total investment of $14.2 million, and we’d be remiss if we don’t mind this in the future.
Most importantly we want to thank the PCaP research subjects that many people believed would not participate in research of this type. It’s just PCaP.org or you can Google North Carolina Louisiana Prostate Cancer Project.
We’d be happy in—how much time left—10 minutes left, okay; we were 5 minutes over but we started 5 minutes late, so we’re perfect. We’d be happy to entertain questions. Do you want to moderate?
Speaker
Good afternoon. I’m Robert Young from Birmingham, Alabama Man to Man. First of all I’d like to commend you because I think—I’m not sure how many people in this room are aware of the Tuskegee Study and just—just for clarification how many people are aware of what he was talking about? Well I’m glad to hear that because that—that did have a—that does have a high impact on African American men and prostate cancer and—and doctors.
The first—those two things are very important in the African American community as far as that and diet. So I really want to take the time to commend you for doing that study; a lot of us that’s African Americans are already aware of those factors, but your study is bringing out more to the mainstream people, so I do want to commend you and thank you for doing that study.
James Mohler
Thank you. I want to point out; we have another microphone on this side as well so if you have questions please come up.
Speaker
Ryan Austin, Institute for Systems Biology up in Seattle. I was just going to ask to the extent that the disparities can be attributed to patient/doctor relationship you presume that wouldn’t be specific to prostate cancer, right? You would think that would apply to a number of diseases; have you looked at other diseases and can you comment on that?
Elizabeth Fontham
Good; many others have—have looked at the key role in patient/provider communication in—in an array of diseases. We obviously in this study were interested in prostate cancer. The—the issue is when there is a mismatch by race if a provider is one race and—and the patient is another it makes communication more difficult and it makes trust harder to earn between the two, further complicated obviously by—by not having a usual provider which is—is something that often happens when your best and sometimes only available care is in emergency rooms as opposed to having a medical home with a consistent provider. So it’s not new; we weren't surprised to find it. But we’re very interested in how that part interacts with other host issues and tumor issues.
James Mohler
If I could just comment further on that; the—the first step in addressing this problem is recognizing it and then quantitating it and developing interventions to educate providers and you can say making the consumer a more intelligent consumer. This works best ways—both the patient and the physician have to be more sensitive to these differences.
Elizabeth Fontham
If I add one sentence—that the good news is many schools of medicine and nursing schools and others who train health care providers are now incorporating cultural competency into their curriculum. And this will not be an instant cure but it’s very important.
Speaker
Cathy Meade with the Virginia Prostate Cancer Coalition. I am very happy to hear that you’re doing this type of work. As we go out into the community it’s helpful if we have more information about what we need to do, how we need to approach it and—and who should be going out and where we should focus. A couple of years ago, probably it’s been about 8 years ago, I had a conversation with Dr. [Judd] Moul and he had done a—an analysis of the men in the military and what he had found was that the survival benefit, if I remember correctly, the survival benefit for African American men in the military was almost the same as it was for white men, which would mean that if you—if you make everything the same then the outcome would be the same. And I’m very sorry to hear that there’s not going to be enough money available for you to carry this on long enough to potentially find out if there is a survival benefit.
James Mohler
Now let me just say that Judd’s study was extremely important and there are—there are other studies that suggest that survival differences persist after correction for everything between the races. But his study certainly suggests that it’s the health care interaction which when we planned PCaP was my belief at the time. There’s still—we still need to sort out what are the portions of this that go into each of the three buckets so we can know where to invest our health care dollars. We are continuing PCaP; we are writing grants. I was working on one in my room this morning in collaboration with an investigator at the University of Connecticut. We have two just been funded, not yet with award notices to young investigators. So everyone in this room can help us keep PCaP going. This is very similar to the UNC Lineberger Breast Cancer Study that was the first SPORE funded and they had like five papers in its first 10 years and now they just crossed the 250 publication mark. All these population-based studies start slowly and then become a factory for publication, right Terri?
Elizabeth Fontham
I would also like to say—oops, this is the one that’s on—I would add that Louisiana is an NCI-funded SEER tumor registry and by definition those tumor registries must do annual mortality status and—and follow-up. So for our Louisiana study subjects we will be able to record link to the tumor registry by name and—and we will know survival rates for those 1,200-plus men.
Speaker
Okay; we’ve got a question in the back here.
Speaker
My name is Rudy Lombard and I’m a native of New Orleans, so I find this study absolutely fascinating. But I’d like to know in addition to all those wonderful universities, what is the reason none of the HBCUs were included in the study.
James Mohler: You want the short answer? I didn't know what an HBCU—
Speaker: Well I'm not sure—.
James Mohler
I didn't know what an HBCU was in 2002. And this application there was a very narrow time line for preparation and basically what the study represents is me and all my friends.
Speaker
Okay; well for people who don’t know what an HBCU is it’s a historically black college and university, so next time keep us in mind.
Elizabeth Fontham
I want to—I want to add since I was on the Louisiana end of things, we have been working with Xavier. There is a disparities conference that’s coming up and we’ve been asked to make a presentation about the follow-up study. We have also worked with their School of Pharmacy on some related projects and as part of the Louisiana Cancer Research Consortium which is comprised of Xavier and LSU and Tulane and Oxnard, we are encouraging utilization of the data and the specimens that we have. And so I’m very hopeful that they will be able to use and learn from—from data that is readily available.
Speaker
Okay; we’re going to try to get—-we’re really running out of time. We have three more; we’re going to try to get those three and then we have an announcement as well, so please—.
Speaker
In addition to education and the economic differences, prenatal wasn’t involved which most people don’t know how impact—that impacts things and when we go to reach the African—black American community there’s a cultural thing about digital rectal exam and a masculinity thing that has ignorance rampant and distrust based on the syphilis experiment with Tuskegee. It keeps people totally away.
James Mohler
Yeah; you raise a very good point and it is very interesting to us that we were able to enroll men in spite of how prevalent Tuskegee is. There was no difference by race in either state. This digital rectal exam problem is one I think of education and there—national statistics show that the racial difference in the proportion of men who have had a digital rectal exam in the last 3 years has essentially disappeared. So I think your concern is correct, but I think it’s going away. I hope it is.
Speaker
The first question—[Lucia Languino], Thomas Jefferson University. What is the mechanism to obtain specimens and data that have been collected and I guess you mentioned right now that we can have access and you would like to distribute them, but how do we request them?
James Mohler
Right; so you go right to the website and there is a public access portion to it for our research subjects and potential collaborators and it’s very simple. Click, click, click; if you have any trouble at all you ask Bonnie Blackard for assistance. We have a very user-friendly pathway. The application, the initial application to use our specimens is two pages and it’s almost all filled out by clicking. So we’re very user-friendly; see the website and call Bonnie if you have a problem.
Speaker
Is the application—sorry; is the application rejected sometimes? Are there reasons why it will be rejected or should we hear about this—?
James Mohler
We’ve now evaluated about 50 applications and I think we’ve only rejected two. The other thing we do is work with you all. As I mentioned I have a very junior investigator at U-Conn that I’m not even going to be a part of this grant; I’m just a consultant. I’ve totally rewritten significant portions of the grant. That’s the help we provide from our rather senior investigators.
Speaker
Okay; I’m Harold Decarli from the First State Prostate Cancer Support Group. My son is a health care provider. He’s an internist and I have to speak for his situation. He is a provider not in an affluent area and it’s—it’s a problem that—that he—that I hear from him. People don’t know what medication they’re taking, they don’t know who their doctor was that they just saw; there are all kinds of problems that—that the patients bring to the physicians that really handicaps the physician. I just wanted to share that with everyone.
James Mohler
Right; there is clear that we need a different health care system in America. There’s no doubt about that. I want to mention that the—the U-Conn person that I mentioned is actually—Terri is the PCaP PI for her and has been mentoring. I just took my red pen to her grant and so Terri has had the major effort. But the point I want to make is that we are here to help you all use these biospecimens.