Epidemiology of prostate cancer
Epidemiology and Molecular Pathology of Cancer: Bootcamp course
Tuesday, 3 January 2012
Learning Objectives
To describe clinical presentation of prostate cancer
To present descriptive epidemiology of prostate cancer
To give overview of risk factors for prostate cancer and opportunities for prevention of lethal disease
Clinical presentation
The Prostate
Clinical synopsis
99% of cancers are epithelial adenocarcinoma Symptoms
Urinary frequency, urgency, nocturia, bone pain Majority of cancers diagnosed now have no symptoms
Diagnosis Digital rectal exam Prostate specific antigen (PSA) screening/testing Biopsy of prostate
Treatment Radical prostatectomy Radiation Watchful waiting Hormonal therapy either as primary or adjuvant treatment
Stage and Grade
Gleason Grade (2-10)TNM*-stage
* T=tumor, N=node, M=metastases
Descriptive epidemiology
The burden of prostate cancer
Latent prostate cancer
Prostate cancer reservoir in men dying from causes other than prostate cancer and who were not known to have prostate cancer during life
Welch, JNCI J Natl Cancer Inst 2010;102:605-613
Trends in prostate cancer incidence over time
IARC, 2008
USA
Sweden
Italy
Japan
Trends in prostate cancer mortality over time
USA
Sweden
Italy
Japan
IARC, 2008
Greece
Risk factors
Older age as a risk factor
IARC, Cancer Mondial, CI5plus
Race/Ethnicity as a risk factor
SEER Registry, http://seer.cancer.gov/statfacts/html/prost.html
0 50 100 150 200 250 300
White
Black
Asian/PI
Native American
Hispanic
ASR per 100,000
Incidence
Mortality
2.4x greater mortality for blacks vs. whites
0
2
4
6
8
10
12
14
Father Brother Father +Brother
Affected family member
Re
lati
ve
ris
k (
95
% C
I)
Family history as a risk factor
Hemminki CEBP 2002
GWAS and prostate cancer
Thomas G, Nature Genetics 2008
Risk factors for prostate cancer in HPFS (1986-2002)
Incident Non-
advanced Low-grade
Fatal Advanced High-grade
Vigorous activity
Body mass index
Calorie intake
Height
Tobacco (last 10y)
Tomato sauce
-linolenic acid
Calcium
Giovannucci, Int J Cancer 2007
Model of prostate cancer development and progression
RISK OF AGGRESSIVE PROSTATE CANCERLETHAL PROSTATE CANCER
Pathways: Energy Balance/Insulin * Inflammation * Vitamin D signaling
Factors: Obesity * Physical inactivity * Infection * Coffee * Low vitamin D
Overview of factors
Current Hypotheses1.Obesity and weight change
2.Physical activity
Novel hypotheses
1.Infections
2.Coffee
3.Vitamin D
Obesity and Physical activity
Obesity and weight change
Obesity and weight change
Obesity and weight change
Obesity and weight change
Obesity is associated with: Higher levels of insulin Lower levels of adiponectin Lower levels of testosterone Higher levels of inflammatory cytokines
Obesity and prostate cancer survival
Physicians’ Health Study
•2,500 men with prostate cancer
•Obesity at baseline
•Followed for up to 28 years
Excess body weight could account for 33.7% of PCa death
Insulin, obesity and lethal prostate cancer
Weight change and risk of cancer recurrence
Does walking lower risk of PCa progression? Prostate cancer progression
Richman E, 2011 Cancer Res
Relative risk of prostate cancer progression associated with walking pace and duration among 1275 men with cancer
< 3 mph
≥ 3 mph
< 3 mph
≥ 3 mph
Infections
LocalInflammation
Infections
PROSTATE CANCER
PROGRESSION
Trichomonas vaginalis and prostate cancer
Common non-viral sexually transmitted infection
Mostly asymptomatic in men
Infections can reach prostate
Repeated infections do not confer immunity
Study design
Physicians’ Health Study
1982
Blood samples from 14,916 participants
2000
1,116 men diagnosed
with prostate cancer
2008
673 cancer cases673 controls
Follow-up for
metastases &
mortality
T vaginalis and risk of advanced prostate cancer
0%
10%
20%
30%
40%
50%
Controls Cases
Relative risk : 2.2 (95% CI: 1.1, 4.4)
% T
. vag
inalis
sero
posit
ive
Stark et al, JNCI 2009
T vaginalis and risk of lethal disease
Relative risk: 2.7 (95% CI: 1.4, 5.3)
% T
. vag
inalis
sero
posit
ive
Stark et al, JNCI 2009
Coffee
Coffee and prostate cancer risk
Insulin Inflammation Antioxidants
Coffee
Prostate cancer progression
All prostate cancer Lethal cancer Nonlethal cancer
ptrend=0.10 ptrend=0.004 ptrend=0.77
RR=0.40 (0.28-0.77)
RR=0.93 (0.74-1.16)
RR=0.82(0.68-0.98)
Coffee and prostate cancer risk
Wilson et al, JNCI 2011
Regular vs. Decaf
Lethal cancer
Regular CoffeeRR=0.56 (0.28-1.11)
Decaf CoffeeRR=0.59 (0.36-0.96)
Vitamin D
41
The Vitamin D pathway
CYP27A1
CYP27B1VDR
Differentiation Apoptosis Cell-cycle
Anti-angiogenesis
CYP24A1
Vitamin D and lethal prostate cancer
Circulating levels of vitamin D: High vitamin D 40 percent lower risk of lethal
prostate cancer
Vitamin D in tumors: High expression of receptor in tumor 70 percent
lower risk of lethal prostate cancer
Genetic variants in vitamin D pathway Significantly associated with lethal prostate cancer
Summary
Prevention of lethal prostate cancer
Risk factor Association Prevention
Obesity Weight loss
Physical activity Walking
Infections Treatment; anti-inflammatory
Coffee
Vitamin D Supplements; Sun