Elizabeth Radke, MPHFaina Linkov, PhD

University of Pittsburgh Cancer Institute

BackgroundMost 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

SurvivalFive year survival rates for local and regional

stages are essentially 100%For distant metastases, five year survival is

only 34%

DemographicsMedian 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 subcontinent2.9 per 100,000 men in China

Highest rates occur in Western Europe, Australia, and North America107.8 and 185.4 per 100,000 white and black

men in the United StatesMigration 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 VegetablesSome 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 – ProteinSoy

Possible decrease in prostate risk with increased soy intake

Red meat and processed meatConsumption of red or processed meat has been

associated with a higher risk of total or advanced prostate cancer in some cohort studies

FishSome 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 FactorsAspirin and Non-Steroidal Anti-Inflammatory

AgentsWeak inverse association between regular anti-

inflammatory use and prostates cancerVasectomy

Some studies have shown increased risk following vasectomy

Occupational and Environmental ExposuresPesticide use High electromagnetic field exposure

STD Infection

Family HistoryRelative risk for having either a father or

brother with prostate cancer ranges from 2-3Risk is higher with increasing number of first-

degree relatives with diseaseHigher concordance for prostate cancer

diagnosis between monozygotic than dizygotic twins

Segregation analyses support an autosomal dominant mode of inheritanceGene(s) is not yet identified

Genetic FactorsSex Steroid Hormones and Hormone

Metabolizing EnzymesPolymorphisms in Vitamin D Receptor GeneGrowth FactorsInfection and Response to Infection

(Inflammation)Sexually transmitted infectionsProstatitis

Biotransformation Enzymes

Screening and Early DetectionIn 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 67.5-80%, 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

50

75

100

125

150

175

200

225

2501975

1980

1985

1990

1995

2000

10

11

12

13

14

15

PSA and Prostate Cancer Incidence and Mortality(U.S. 1975-2000)

Source: Surveillance, Epidemiology, and End Results Program, 1975-2000, Division of Cancer Control and Population Sciences, National Cancer Institute, 2003.

Incid

en

ce

PSA Screening

Morta

lity

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 DirectionsEtiology

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)

ReferencesCancer Epidemiology, 3rd ed. 2006. Oxford

University PressCenters for Disease ControlAmerican Cancer SocietyLecture by Donald Vander Griend, PhD,

University of Chicago Urology Research Laboratory