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Epidemiology of prostate cancer

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

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Epidemiology of prostate cancer

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  1. Epidemiology of prostate cancer Epidemiology and Molecular Pathology of Cancer: Bootcamp course Tuesday, 3 January 2012

  2. 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

  3. Clinical presentation

  4. The Prostate

  5. 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

  6. Stage and Grade TNM*-stage Gleason Grade (2-10) * T=tumor, N=node, M=metastases

  7. Descriptive epidemiology

  8. The burden of prostate cancer

  9. 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

  10. Trends in prostate cancer incidence over time USA Sweden Italy Japan IARC, 2008

  11. Trends in prostate cancer mortality over time Sweden USA Italy Greece Japan IARC, 2008

  12. Risk factors

  13. Older age as a risk factor IARC, Cancer Mondial, CI5plus

  14. Race/Ethnicity as a risk factor 2.4x greater mortality for blacks vs. whites SEER Registry, http://seer.cancer.gov/statfacts/html/prost.html

  15. Family history as a risk factor Hemminki CEBP 2002

  16. GWAS and prostate cancer Thomas G, Nature Genetics 2008

  17. Risk factors for prostate cancer in HPFS (1986-2002) Giovannucci, Int J Cancer 2007

  18. Model of prostate cancer development and progression Factors: Obesity * Physical inactivity * Infection * Coffee * Low vitamin D Pathways: Energy Balance/Insulin * Inflammation * Vitamin D signaling RISK OF AGGRESSIVE PROSTATE CANCER LETHAL PROSTATE CANCER

  19. Overview of factors Current Hypotheses • Obesity and weight change • Physical activity Novel hypotheses • Infections • Coffee • Vitamin D

  20. Obesity and Physical activity

  21. Obesity and weight change

  22. Obesity and weight change

  23. Obesity and weight change

  24. 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

  25. 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

  26. Insulin, obesity and lethal prostate cancer

  27. Weight change and risk of cancer recurrence

  28. Does walking lower risk of PCa progression? • Prostate cancer progression Relative risk of prostate cancer progression associated with walking pace and duration among 1275 men with cancer Richman E, 2011 Cancer Res < 3 mph ≥ 3 mph

  29. Infections

  30. Infections Local Inflammation PROSTATE CANCER PROGRESSION

  31. 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

  32. Study design Follow-up for metastases & mortality 673 cancer cases 673 controls 1,116 men diagnosed with prostate cancer Blood samples from 14,916 participants 1982 2000 2008 Physicians’ Health Study

  33. T vaginalis and risk of advanced prostate cancer Relative risk : 2.2 (95% CI: 1.1, 4.4) % T. vaginalis seropositive Stark et al, JNCI 2009

  34. T vaginalis and risk of lethal disease Relative risk: 2.7 (95% CI: 1.4, 5.3) % T. vaginalis seropositive Stark et al, JNCI 2009

  35. Coffee

  36. Coffee and prostate cancer risk Coffee  Insulin  Inflammation  Antioxidants  Prostate cancer progression

  37. Coffee and prostate cancer risk All prostate cancer Lethal cancer Nonlethal cancer ptrend=0.77 ptrend=0.10 ptrend=0.004 RR=0.82 (0.68-0.98) RR=0.40 (0.28-0.77) RR=0.93 (0.74-1.16) Wilson et al, JNCI 2011

  38. Regular vs. Decaf Lethal cancer Regular Coffee RR=0.56 (0.28-1.11) Decaf Coffee RR=0.59 (0.36-0.96)

  39. Vitamin D

  40. The Vitamin D pathway Differentiation Apoptosis Cell-cycle Anti-angiogenesis 41 CYP27A1 VDR CYP27B1 CYP24A1

  41. 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

  42. Summary

  43. Prevention of lethal prostate cancer

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