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Mechanism for link between high fat diet and risk of prostate cancer and disorders unveiled

Prostate cancer is the second leading cause of cancer-related deaths in men with an estimated 192,280 new cases diagnosed in the US in 2009 (Jemal 2009). Diet is considered one of the most important controllable risk factors for inflammation and prostate diseases including benign prostatic hyperplsia (BPH), prostatitis, and prostate cancer.

Sanjay Gupta, MS, PhD, Carter Kissell associate professor & research director in the Department of Urology and associate professor in the Department of Nutrition in the Case Western Reserve School of Medicine, and his team of post-doctoral fellows have focused on understanding the mechanisms of the deleterious effects of a high fat diet on the prostate.

Previously, Dr. Gupta's team demonstrated that nuclear factor kappa B (NF-ƒÛB), a protein complex that controls DNA transcription which is activated as a result of inflammation and stress, is constitutively activate in human prostate adenocarcinoma and is related to tumor progression (Shukla S et al, Neoplasia, 2004).

In a study, "High Fat Diet Increases NF-ƒÛB Signaling in the Prostate of Reporter Mice", released online today in the journal "The Prostate" (, Dr. Gupta and his team demonstrate that a high fat diet results in activation of NF-ƒÛB in the abdominal cavity, thymus, spleen, and prostate (Vykhovanets et al, The Prostate, 2010). Non obese NF-ƒÛB reporter mice were fed a high fat diet for four, eight, and 12 weeks. Compared with mice fed a regular diet, the high fat diet group had significant increases in prostate weight, and in the prostate expression of markers of oxidative stress (such as NADPH), and inflammation (such as the downstream targets of NF-ƒÛB: nitric oxide synthase, and cyclooxygenase [COX-2]) were increased. These studies provide direct evidence that a high fat diet causes proliferation, inflammation, and oxidative stress that can lead to benign prostatic hyperplasia, prostatitis, and cancer of the prostate, some of the most common disorders affecting adult men.

"Our studies provide evidence that a high-fat diet increases the activation of NF-ƒÛB along with elevated levels of NADPH oxidase components which might lead to intraprostatic inflammation. This study strengthens the link between a high-fat diet¡Xtypical of "Western style" high fat diet¡Xas a potential cause of prostatic diseases including BPG and prostate cancer," said Dr. Gupta.

This work was supported by grants from the National Cancer Institute, the National Center for Complementary and Alternative Medicine, and the Sullivan Foundation for the Study of Prostatitis.

About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the school of medicine.

Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 20 among U.S. research-oriented medical schools as designated by U.S. News &World Report "Guide to Graduate Education."

The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002.

Christina DeAngelis | EurekAlert!
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