Research: Prostate Cancer Center of Excellence
Recent Accomplishments in Research
There is a rich bounty from the scientists who participate in the Prostate Cancer Center of Excellence (PCCOE). Recent findings from the group of Jiangeng Xu, PhD, MD, exemplified by recent papers in the New England Journal, have two other, notable findings with translational importance, from the fields of animal models and molecular epidemiology include the findings of Yong Chen, PhD, and Gary Schwartz, PhD.
Omega-3 and Prostate Cancer
The first of these comes from the lab of Yong Chen, PhD, who directs a Program Project grant in the area of prostate cancer and fatty acids (described in Berquin IM, Min MY, Wu J, Perry D, Cline JM, Thomas MJ, et al., Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. Journal of Clinical Investigation 2007;117:1866-1875.)
The JCI study from Dr. Chen’s lab is based on epidemiologic observations that suggest that diets rich in omega-3 polyunsaturated fatty acids are associated with a lower incidence of prostate cancer. To determine the influence of fatty acids on prostate cancer risk in animals with a defined genetic lesion, Dr. Chen’s group used prostate-specific Pten-knockout mice, an immune-competent, orthotopic prostate cancer model, and diets with defined polyunsaturated fatty acid levels. They found that omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival. Conversely, opposite effects were seen with omega-6 fatty acids. Tumors from mice on the omega-3 diet had lower proportions of phosphorylated Bad and higher apoptotic indexes compared with those from mice on omega-6 diet. Knockdown of Bad eliminated omega-3-induced cell death, and introduction of exogenous Bad restored the sensitivity to omega-3 fatty acids. These data suggest that modulation of prostate cancer development by polyunsaturated fatty acids is mediated in part through Bad-dependent apoptosis. This study has important translational implications for dietary chemoprevention of prostate cancer.
Calcium Levels and Prostate Cancer
A second notable finding is the observation made in two prospective nationally representative studies that serum levels of calcium that are normal, but are high (high normocalcemia) significantly predict fatal prostate cancer. This observation was reported by Halcyon G. Skinner, PhD, and Dr. Gary Schwartz (Scientific Director of the PCCOE), Skinner HG, Schwartz GG. A prospective study of total and ionized serum calcium and fatal prostate cancer. Cancer Epidemiol Biomark Prev 2009; 18:575-578. In 2008, these authors reported a significant positive association in the National Health and Nutrition Examination Survey between high levels of total calcium in serum, measured prospectively, and risk of fatal prostate cancer. This study sought to confirm that original observation. To do so, Drs. Skinner and Schwartz examined associations between total and ionized serum calcium and prostate cancer mortality in an independent cohort, the Third National Health and Nutrition Examination Survey. 25 prostate cancer deaths occurred over 56,625 person-years of follow-up. Compared with men in the lowest tertile of total serum calcium, the multivariate-adjusted relative risk for death from prostate cancer for men in the highest tertile was 2.07 (95 percent confidence interval, 1.06-4.04). For ionized serum calcium, the physiologically active fraction of total serum calcium, the relative risk for men in the highest tertile was 3.18 (95 percent confidence interval, 1.09-9.28). These findings support the hypothesis that serum calcium is a prospective biomarker of fatal prostate cancer. These findings are important because there is a pressing need to discriminate the minority of prostate cancers that will become lethal from the majority that are unlikely to do decide which cancers require treatment.
The recent recruitments of a genitourinary-specialty trained pathologist, Joseph Sirintrapun, MD, and a clinician-scientist, KC Balajii, MD, both act to accelerate translational research. For example, although he has been at Wake Forest for only several months, Dr. Sirintrapun is already a participant on several funded projects.