Elizabeth Radke, MPH Faina Linkov, PhD University of Pittsburgh Cancer Institute

Background Most commonly diagnosed cancer in American men Incidence rate=168.9 per 100,000 men Third most common cause of cancer death in the U.S. Mortality rate = 33.9 per 100,000 men Incidence rates soared in the early to mid 1990s when widespread screening for PSA was instituted

Prostate cancer 2008 (estimate) New cases: 186,32 Deaths: 28,660

Survival Five year survival rates for local and regional stages are essentially 100% For distant metastases, five year survival is only 34%

Demographics Median age at prostate cancer diagnosis is 71 in whites and 69 in blacks Has dropped slightly since introduction of PSA screening African-Americans have the highest incidence and mortality rates Incidence and mortality in Asian/Pacific Islanders, American Indians, and Hispanics are substantially lower than whites Incidence and mortality are positively correlated with the gross national product

Prostate Cancer Incidence Rates, by State, 2004

International Patterns Lowest rates are observed in the Far East and on the Indian subcontinent 2.9 per 100,000 men in China Highest rates occur in Western Europe, Australia, and North America and per 100,000 white and black men in the United States Migration studies show that men of Asian heritage living in the U.S. are at lower risk than white Americans but greater risk than men of similar ancestries living in Asia

Diet – Fruits and Vegetables Some studies have shown decreased risk of prostate cancer with increased intake of vegetables, but these findings are inconsistent Tomatoes Overall data indicate that the intake of tomatoes (associated with higher circulating concentrations of lycopene) is associated with lower risk of prostate cancer Brassica or Cruciferous vegetables (Broccoli, etc.) Small number of studies suggest inverse association between eating brassica vegetables and prostate cancer

Diet – Protein Soy Possible decrease in prostate risk with increased soy intake Red meat and processed meat Consumption of red or processed meat has been associated with a higher risk of total or advanced prostate cancer in some cohort studies Fish Some studies have shown protective effect of eating fish regularly, mostly attributed to omega-3 fatty acids

Diet – Other Association between fat consumption and prostate cancer has been observed in some studies Countries with greater per capita milk consumption have higher prostate cancer mortality rates No significant association between smoking and alcohol use has been observed

Other Factors Aspirin and Non-Steroidal Anti-Inflammatory Agents Weak inverse association between regular anti- inflammatory use and prostates cancer Vasectomy Some studies have shown increased risk following vasectomy Occupational and Environmental Exposures Pesticide use High electromagnetic field exposure STD Infection

Family History Relative risk for having either a father or brother with prostate cancer ranges from 2-3 Risk is higher with increasing number of first-degree relatives with disease Higher concordance for prostate cancer diagnosis between monozygotic than dizygotic twins Segregation analyses support an autosomal dominant mode of inheritance Gene(s) is not yet identified

Genetic Factors Sex Steroid Hormones and Hormone Metabolizing Enzymes Polymorphisms in Vitamin D Receptor Gene Growth Factors Infection and Response to Infection (Inflammation) Sexually transmitted infections Prostatitis Biotransformation Enzymes

Screening and Early Detection In 2001, 75 % of American men aged 50 years or older reported that they had every had a PSA test, 54% had recently had one Efficacy of screening to detect prostate cancer at an earlier stage than digital rectal exam has been shown Sensitivity of PSA test is roughly %, Specificity is 60-70% Many false positives With PSA concentration over 4 ng/mL, most men will receive work-up including prostate biopsy

Diagnosing Prostate Cancer DETECTING PROSTATE CANCER  PSA  Kallikrein Tumor Markers  Digital Rectal Exam  Biopsy STAGING PROSATE CANCER  The TNM staging system  Histologic Grading: The Gleason Score  Post-Surgical Evaluation  Imaging Bone Metastases

PSA and Prostate Cancer Incidence and Mortality (U.S ) Source: Surveillance, Epidemiology, and End Results Program, , Division of Cancer Control and Population Sciences, National Cancer Institute, Incidence PSA Screening Mortality

What is PSA?  Prostate-Specific Antigen  An antigen is something an antibody binds to.  Member of the Kallikrein protease family.  Vast majority of PSA in our body is produced by secretory prostate epithelial cells.  Also made in very low amounts in the breast, thyroid, and placenta, among others.

Future Directions Etiology Role of factors such as obesity Genetic factors Role of different nutrients Role of chronic intraprostatic inflammation Excess risk in African-Americans Early detection (improve specificity)

References Cancer Epidemiology, 3 rd ed Oxford University Press Centers for Disease Control American Cancer Society Lecture by Donald Vander Griend, PhD, University of Chicago Urology Research Laboratory