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Epidemiology of Bladder Cancer Jennifer Prescott, PhD Epidemiology and Molecular Pathology of Cancer: Bootcamp Course Thursday, January 12, 2012.

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Presentation on theme: "Epidemiology of Bladder Cancer Jennifer Prescott, PhD Epidemiology and Molecular Pathology of Cancer: Bootcamp Course Thursday, January 12, 2012."— Presentation transcript:

1 Epidemiology of Bladder Cancer Jennifer Prescott, PhD Epidemiology and Molecular Pathology of Cancer: Bootcamp Course Thursday, January 12, 2012

2 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

3 Descriptive Epidemiology

4 Global Incidence

5 ASR per 100,000

6 United States, 2011 Siegel et. al CA: A Cancer Journal for Clinicians #12 Urinary bladder 17,230 2% #13 Urinary bladder 4,320 2%

7 Trend in US Incidence Rates

8 Trend in US Mortality Rates

9 Subtype Distribution in US population >90% transitional cell carcinoma (TCC) 5% squamous cell carcinoma (SCC) 1% adenocarcinoma Other rare subtypes

10 Survival by SEER Stage

11 Established Risk Factors

12 Crude Age-specific Incidence Rates

13 Incidence by Race and Sex

14 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

15 Urogenous-contact hypothesis Ureters Bladder Urethra

16 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 International Journal of Cancer

17 Smoking Dose Number of cigarettes/day Brennan et. al International Journal of Cancer

18 Smoking Duration Years of smoking Brennan et. al International Journal of Cancer

19 Smoking Cessation Years since quitting Brennan et. al International Journal of Cancer

20 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

21 Suspected Risk/Protective Factors

22 Reduce effect of carcinogen Ureters Bladder Urethra DNA adducts - OR -

23 Health Professionals Follow-up Study (HFPS) 1986 (51,000 men) Diet

24 Fluid Intake in HPFS men Michaud et. al New England Journal of Medicine*Literature not consistent Table 4.

25 Coffee In 1991, classified as possible bladder carcinogen by International Agency for Research on Cancer

26 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 Cancer Causes and Control

27 Coffee Cups per day Sala et. al Cancer Causes and Control Table 4. from Michaud et. al New England Journal of Medicine

28 Fruits & Vegetables Source of phytochemicals Induce detox enzymes Antioxidants

29 Fruits & Vegetables Michaud et. al Journal of the National Cancer Institute

30 Fruits & Vegetables Published literature ▫Overall associated with reduced risk ▫No consistent association with subcategories ▫No consistent association with micronutrients

31 Gonorrhoea Michaud et. al British Journal of Cancer Consistent with 2 case-control studies of invasive TCC

32 Non-Steroidal Anti-Inflammatory Drugs Genkinger et. al International Journal of Cancer

33 Genetic Epidemiology

34 Genetic Contribution Family history ▫~2 fold risk ▫Bladder cancer families rare No high-penetrance mutations

35 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 Lipophilic Toxins Reactive Intermediates Water-soluble compound Phase IPhase II

36 Blood subcohorts 1986 (51,000 men) ,000 Blood (120,000 women) ,000 Blood HPFS NHS

37 Bladder Cancer GWAS Study Design Rothman et. al Nature Genetics

38 Confirm prior GWAS results Rothman et. al Nature Genetics

39 Novel GWAS loci Rothman et. al Nature Genetics

40 NAT2-smoking interaction Rothman et. al Nature Genetics

41 Urea transporter locus Garcia-Closas et. al Human Molecular Genetics (above table) Rafnar et. al Human Molecular Genetics

42 Gene-gene interaction? Garcia-Closas et. al Human Molecular Genetics

43 Recurrence and Progression

44 Survival by SEER Stage

45 Recurrence and Progression Non-muscle invasive bladder cancer (NMIBC) ▫50 – 70% with at least 1 recurrence  Most within 3 years ▫10 – 30% progress

46 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 $$$

47 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

48 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

49 Harvard Cohorts Health Professionals Follow-up Study ▫http://www.hsph.harvard.edu/hpfs/http://www.hsph.harvard.edu/hpfs/ Nurses’ Health Study I and II ▫http://www.channing.harvard.edu/nhs/http://www.channing.harvard.edu/nhs/ Nurses’ Health Study III (NEW!) ▫http://www.nhs3.org/http://www.nhs3.org/


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