epidemiology of bladder cancer
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Epidemiology of Bladder Cancer. Jennifer Prescott, PhD Epidemiology and Molecular Pathology of Cancer: Bootcamp Course Thursday, January 12, 2012. Learning Objectives. To review descriptive epidemiology of bladder cancer To understand etiology behind established bladder cancer risk factors - PowerPoint PPT PresentationTRANSCRIPT
Epidemiology of Bladder CancerJennifer Prescott, PhDEpidemiology and Molecular Pathology of Cancer:Bootcamp Course
Thursday, January 12, 2012
Learning Objectives
•To review descriptive epidemiology of bladder cancer
•To understand etiology behind established bladder cancer risk factors
•To recognize opportunities for epidemiologic research of bladder cancer
Descriptive Epidemiology
Global Incidence
Global Incidence
ASR per 100,000
United States, 2011
Siegel et. al. 2011 CA: A Cancer Journal for Clinicians
#12 Urinary bladder 17,230 2%
#13 Urinary bladder 4,320 2%
Trend in US Incidence Rates
http://seer.cancer.gov/
19751977
19791981
19831985
19871989
19911993
19951997
19992001
20032005
20070
5
10
15
20
25
30
35
40
Male Female
Year of Diagnosis
Rat
e pe
r 10
0,00
0
Trend in US Mortality Rates
http://seer.cancer.gov/
19751977
19791981
19831985
19871989
19911993
19951997
19992001
20032005
20070
2
4
6
8
10
12
Male (mortality) Female (mortality)
Year of Diagnosis
Rat
e pe
r 10
0,00
0
Subtype Distribution in US population
•>90% transitional cell carcinoma (TCC)
•5% squamous cell carcinoma (SCC)
•1% adenocarcinoma
•Other rare subtypes
In situ Localized Regional Distant Unknown0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100% 96.6%
70.7%
34.6%
5.4%
49.1%
5-year Relative Survival
Survival by SEER Stage
http://seer.cancer.gov/
Established Risk Factors
Crude Age-specific Incidence Rates
15-1920-24
25-2930-34
35-3940-44
45-4950-54
55-5960-64
65-6970-74
75-7980-84 85+
0
50
100
150
200
250
300
350
400
Male Female
Age at Diagnosis
Rat
e pe
r 10
0,00
0
http://seer.cancer.gov/
Incidence by Race and Sex
Male Female0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
45.0
White
Black
Hispanic
Asian / Pacific Is-lander
American Indian / Alaska NativeR
ate
per
100,
000
http://seer.cancer.gov/
Carcinogen exposure and TCC• Occupation
▫Workers in dye and rubber industries▫Accounts for 5 to 10% of cases
• Smoking▫Most important risk factor ▫Same effect in males and females▫Accounts for 1/2 male, 1/3 female cases
• Aromatic amines induce DNA adducts▫4-aminobiphenyl, 2-naphthylamine, benzidine
Urogenous-contact hypothesisUreters
Bladder
Urethra
Smoking and Bladder Cancer in Men•Pooled analysis
▫11 case-control studies▫European countries
•2,600 Cases▫Histologically confirmed▫Incident (recruited within short time after dx)
•5,524 Controls▫3 population-based, 7 hospital-based, 1 both▫Hospital controls with non-smoking related
diseases
Brennan et. al. 2000 International Journal of Cancer
Smoking Dose
Never 1-2 3-4 5-910-14
15-1920-24
25-2930-34
35-3940+
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
5.00
1.04
1.80
2.75
3.44
4.50 4.514.74
4.61
3.99
4.29
Odd
s R
atio
Number of cigarettes/dayBrennan et. al. 2000 International Journal of Cancer
Never
1-4 5-9 10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60+0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
1.21
1.66
2.21
3.81
4.684.96
6.14
Odd
s R
atio
Smoking Duration
Years of smokingBrennan et. al. 2000 International Journal of Cancer
Smoking Cessation
Years since quittingBrennan et. al. 2000 International Journal of Cancer
Current 1-4 5-9
10-1415-19
20-2425+
Never0.00
0.20
0.40
0.60
0.80
1.00
1.20
0.6500000000000010.6700000000000010.610000000000001
0.46 0.45
0.37
0.2
Odd
s R
atio
Chronic Inflammation and SCC•Schistosoma haematobium
▫Endemic in Middle East and parts of Africa▫Ova found in bladder wall▫Infestation control -> lower rates of SCC
•Indwelling catheters▫Patients with spinal cord injury
•Reactive oxygen and nitrogen species
Suspected Risk/Protective Factors
Reduce effect of carcinogenUreters
Bladder
UrethraDNA adducts
- OR -
Health Professionals Follow-up Study (HFPS)
1986 (51,000 men)
19881990
19921994
19961998
20002002
20042006
20082010
Diet
Fluid Intake in HPFS men
Michaud et. al. 1999 New England Journal of Medicine *Literature not consistent
Table 4.
Coffee•In 1991, classified as possible bladder carcinogen
by International Agency for Research on Cancer
Coffee• Pooled analysis
▫10 case-control studies▫European countries
• 564 Cases▫Histologically confirmed▫Incident▫Never smokers
• 2929 Controls▫3 population-based, 6 hospital-based, 1 both▫Never smokers
Sala et. al. 2000 Cancer Causes and Control
Coffee
Cups per dayNever 1-2 3-5 6-9 10+
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
1.0 1.0 1.0
1.8
Odd
s R
atio
Sala et. al. 2000 Cancer Causes and Control
Table 4. from Michaud et. al. 1999 New England Journal of Medicine
Fruits & Vegetables
•Source of phytochemicals
•Induce detox enzymes
•Antioxidants
Fruits & Vegetables Michaud et. al. 1999 Journal of the National Cancer Institute
Fruits & Vegetables
•Published literature▫Overall associated with reduced risk
▫No consistent association with subcategories
▫No consistent association with micronutrients
Gonorrhoea
Michaud et. al. 2007 British Journal of Cancer
Consistent with 2 case-control studies of invasive TCC
Non-Steroidal Anti-Inflammatory Drugs
Genkinger et. al. 2007 International Journal of Cancer
Genetic Epidemiology
Genetic Contribution•Family history
▫~2 fold risk▫Bladder cancer families rare
•No high-penetrance mutations
Candidate Detoxification Genes
•N-acetyltransferase 2▫N-acetylation of aromatic amines▫50% of whites are ‘slow acetylators’
Higher levels of adducts Potential interaction with smoking
•Glutathione S-transferase mu 1▫Considered to have wide range of substrates▫50% of whites are GSTM1 null
LipophilicToxins
ReactiveIntermediates Water-soluble
compoundPhase I Phase II
Blood subcohorts
1986 (51,000 men)
19881990
19921994
1996
18,000Blood
20082010
1998
1976 (120,000 women)
19781980
19821984
19861988
19901992
19941996
1998
33,000Blood
20082010
HPFS
NHS
Bladder Cancer GWASStudyDesign
Rothman et. al. 2010 Nature Genetics
Confirm prior GWAS results
Rothman et. al. 2010 Nature Genetics
Novel GWAS loci
Rothman et. al. 2010 Nature Genetics
NAT2-smoking interaction
Rothman et. al. 2010 Nature Genetics
Urea transporter locus
Garcia-Closas et. al. 2011 Human Molecular Genetics (above table)Rafnar et. al. 2011 Human Molecular Genetics
Gene-gene interaction?
Garcia-Closas et. al. 2011 Human Molecular Genetics
Recurrence and Progression
In situ Localized Regional Distant Unknown0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100% 96.6%
70.7%
34.6%
5.4%
49.1%
5-year Relative Survival
Survival by SEER Stage
http://seer.cancer.gov/
Recurrence and Progression
•Non-muscle invasive bladder cancer (NMIBC)▫50 – 70% with at least 1 recurrence
Most within 3 years
▫10 – 30% progress
Surveillance Guidelines (NMIBC)•Clinical visits
▫Frequent schedule 3 months for first 2 years 6 months for additional 2-3 years Annually thereafter
▫Symptoms, urinalysis, cystoscopy, urine cytology
•Lifelong follow-up
•$$$
Risk factors for recurrence/progression
• None have been established
• Smoking▫Risk factor most investigated▫May have worse prognosis, but inconclusive
• Fruits & vegetables▫Broccoli intake Tang 2010 Cancer Epidemiology, Biomarkers & Prevention
• Genetic variants▫rs798766[T] (4p16.3; FGFR3 locus) associated with
recurrence Kiemeney 2010 Nature Genetics
Future Directions• Which risk factors vary by stage/aggressiveness of
disease?
• Additional gene-environment/gene interactions?
• What are risk factors for recurrence/progression?▫Pre-diagnosis▫Post-diagnosis
• Risk factors by tumor tissue markers? ▫Stratify tumors into different etiologic groups▫Etiologic evidence for risk factor associations
Harvard Cohorts•Health Professionals Follow-up Study
▫http://www.hsph.harvard.edu/hpfs/
•Nurses’ Health Study I and II▫http://www.channing.harvard.edu/nhs/
•Nurses’ Health Study III (NEW!)▫http://www.nhs3.org/