IMPaCT Investigator Highlights (Text Version) - Dr. Isaac J. Powell

Title: The Influence of Metabolic Syndrome on Prostate Cancer Progression and Risk of Recurrence in African-American and European-American Men

Investigator: Isaac J. Powell, M.D., F.A.C.S, Wayne State University and Karmanos Cancer Institute

My research is metabolic syndrome and its impact on prostate cancer progression in African Americans compared to European Americans.

Our hypothesis is that the metabolic syndrome impacts on the progression of the disease and may be responsible for the disparity of prostate cancer between African Americans and European Americans. Our focus is to examine the specific features of Metabolic syndrome on prostate cancer among African Americans compared to European Americans. We’re looking at hypertension, obesity, diabetes, hyper-triglyceridemia; that means high fat; and high cholesterol so specifically a low HDL.

So we’re looking at the aggressiveness of the disease as well as the recurrence.

I started out looking at the behavioral issues—why African Americans don’t come in for testing.

Went from that to the biology and the genetics of prostate cancer because we realized that there may be factors there contributing to the disparity and that’s where I am at this time.

We have recruited almost 400 men. We proposed to—to recruit approximately 500 men to this study. The study includes a questionnaire that the men will fill out relating to their medical history, their lifestyles, and health-seeking behaviors.

Then we examine them. We do the height and weight for BMI and then we measure the abdominal girth specifically for the obesity issue. Blood pressure is taken of course because we do that routinely but that’s a part of the metabolic syndrome as well. Blood is also drawn because we’re looking at many genetic factors associated with this.

Eighty percent of the men who we asked to participate in the program actually do, so and that’s pretty good. Actually it’s a little bit higher than 80%, the men that we try to recruit that actually end up participating in the program.

The results we have obtained are preliminary at this time. But when we looked at the features particularly hypertension, African Americans have a higher proportion of high blood pressure. They have a higher proportion of diabetes compared to European Americans. European Americans have a higher proportion of low HDL and then we put it all together to look at metabolic syndrome which required three of the five features to be elevated or abnormal. African Americans did have a—a higher percentage of having metabolic syndrome than European Americans but that number was not statistically significant at this time. With more patients that may become more significant.

Now there’s controversy about diabetes and whether it’s associated with prostate cancer progression. There’s been one report that has shown that in the first 10 years of diabetes, insulin resistance which is the factor that causes the progression of prostate cancer is high.

But after the 10 years, the insulin resistance decreases significantly and diabetes becomes protective. So when you study diabetes, you must separate when they were diagnosed with diabetes if you’re looking at the association with prostate cancer.

We did make one surprising discovery and that is association of hypertension to prostate cancer.

What happens in hypertension is Angiotensin II causes inflammation of the inside of the blood vessels and that causes increase of what we call reactive oxygen species which then causes oxidative stress. Oxidative stress then activates oncogenes; those are cancer genes that then will activate the androgen receptor and that causes proliferation of prostate cancer cells and that’s the mechanism that connects hypertension to prostate cancer.

Our next step is to evaluate the blood specimens from these patients to evaluate the genetics and the biology of this disease and in patients who have metabolic syndrome and those who don’t have metabolic syndrome to see how there are differences. We believe that there’s significant genetic findings that we’re going to appreciate here. We think that we’ll be able to answer a great deal of questions about the biology and the racial disparity.

I think that the question about behavior is an area that needs to be further investigated because we’re still not seeing African Americans enter the health system early enough. What we know is that African Americans are more likely to have a greater proportion of advanced disease and more likely to have it at an earlier age. And so the question is how do we get them to come in at an earlier age and on a greater proportion to be tested for prostate cancer so it can be diagnosed early?

So what we know is that if it is diagnosed early and that we can eliminate or—or certainly reduce the racial disparity, I think that’s the major factor, but if the CDMRP can help resolve that issue I think that will be a major, major step forward in prostate cancer and health care in general.