epidemiology of prostate cancer epidemiology and molecular pathology of cancer: bootcamp course...

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